Rev Esp Quimioter 2012:25(4):240-244

Echinocandins: searching for differences. The example of their use in patients requiring continuous renal replacement therapy                   

N. DE LA LLAMA-CELIS, R. HUARTE-LACUNZA, C. GÓMEZ-BARAZA, I CAÑAMARES-ORBIS, M. SEBASTIÁN- ALDEANUEVA, R. ARRIETA-NAVARRO                                                                            

The echinocandins have a growing role in the treatment of fungal infections because of their novel mechanism of action. This is reflected in recently published management guidelines, but available in vitro data, animal studies, and clinical studies do not clearly differentiate the three agents in class. Comparative clinical efficacy among agents within the class, pharmacokinetic profiles in special populations, pharmacoeconomics justifications, and place in therapy have been largely unanswered. They share many common properties but marketing strategies of drug manufacturers are engaged in product differentiation. Although exist similarities in the pharmacokinetic (PK) profiles of the echinocandins, limited data have been published regarding their pharmacokinetics in continuous renal replacement therapy (CRRT) patients. The pharmacokinetics of drug removal in critically ill patients receiving CRRT is very complex, with multiple variables affecting clearance. This review outlines the basic principles that determine whether a dose adjustment is required. Two studies with data on PK parameters of micafungin and anidulafungin in CRRT patients have been published and are compared following that basic principles in the review.

 

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Rev Esp Quimioter 2012:25(2):100-121

Antibiotheraphy in the 21st century, antibacterials for the second decade. Posibilities or realities in the future? 
           
J. E. GARCÍA-SÁNCHEZ, E. GARCÍA-MERINO, Á.  MARTÍN-DEL-REY, E. GARCÍA-SÁNCHEZ                                                             

 
A review of some antibacterial products is done motivated by the serious situation arisen by the antimicrobial resistance in bacteria. The attention is focus on those drugs with suitable antimicrobial properties that have prospects to be commercialized in the next years because of they are undergoing a clinical development phase (I, II, III). The search for these antibacterial products has been done by an exhaustive study of conference proceedings and web pages of international congresses on chemotherapy, infectious diseases and new antimicrobial drugs. Some of the new antibacterial products acts on known targets, and they belong to already used families. Furthermore, the great majority acts against the gram-positive bacterium. There is also some limited-spectrum antimicrobial drug whose use would minimize the adverse biological effects.
  

 

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Rev Esp Quimioter 2012:25(4):245-251

Pharmacodynamic and pharmacokinetic evaluation of respiratory fluoroquinolones. Guideline to selection of the most appropriate fluoroquinolone                   

J. PARRA-RUIZ, J. HERNÁNDEZ-QUERO                                                                               


Since its approval, fluoroquinolones have become one of the most prescribed antibacterial agents. Because of its widespread use, serious concerns about the emergence of resistance in Streptococcus pneumoniae, Pseudomonas spp, and entrobacteriaceae, has arisen, especially because of cross-resistance between fluoroquinolones.
Huge efforts has been done to identify pharmacokinetic (PK) parameters like maximum serum concentration (Cmax), area under the curve of serum concentrations (AUC) and pharmacodynamic (PD) parameters like the minimum inhibitory concentration (MIC) or the mutant prevention concentration (MPC), to optimize the use of the new fluoroquinolones, especially against these difficult to treat microorganisms.
The new fluoroquinolones commercially available in Spain, levofloxacin and moxifloxacin, have significant differences in their PK (Cmax, half-life, volume of distribution, etc), PD (MIC, MPC,) and in their PK/PD parameters (AUC/MIC; AUC/MPC) that allow clinicians to establish clear preference for the utilization of one of them.
Proper use of these new fluoroquinolones according to these PK/PD parameters will result in better management of respiratory infections with a reduction in the emergence of resistance. Based on data reviewed in this paper moxifloxacin use, with best PK/PD characteristics, should be preferred over levofloxacin. Should levofloxacin be used, alternative dosing strategies would be recommended to avoid selection of resistant variants.  

 

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Rev Esp Quimioter 2012:25(2):122-128

Plasmid-mediated AMPc producing Proteus mirabilis in the Health Care Area of Santiago de Compostela: molecular and epidemiological analysis by rep-PCR and MALDI-TOF 
           

M. TREVIÑO, D. NAVARRO, G. BARBEITO, P. ARESES, C. GARCÍA-RIESTRA, B. J. REGUEIRO                                                               

 
Introduction: Proteus mirabilis is an important pathogen isolated from both community-acquired and health-care associated infections. Acquired AmpC-type beta-lactamases represent an important mechanism of resistance to extended-spectrum cephalosporins and are emerging in several European countries. The objective of this work was to know the prevalence of acquired AmpC beta-lactamase producing P. mirabilis over the last three years and eight months and their clonal relationships comparing MALDI-TOF and automated rep-PCR results.
Methods: P. mirabilis isolates (n= 1,396) were obtained from routine cultures at the University Hospital Complex of Santiago de Compostela from January 2006 to August 2009. Identification to the species level and antimicrobial susceptibility testing were achieved with Vitek 2. The isolates showing intermediate or total resistance to amoxicillin-clavulanic and cefoxitin, cefotaxime or ceftazidime were selected for AmpC phenotypic detection by double-disk synergy test, and molecular confirmation by multiplex PCR. Molecular typing of the isolates was performed by automated rep-PCR and MALDI-TOF.
Results: For the last three years and eight months, the prevalence of AmpC-producing P. mirabilis increased from 0.17% to 4.5%, mainly associated with urinary tract infection in elderly outpatients. In all cases, plasmidic AmpC belonging to LAT/CMY lineage were detected. A high genetic variability was seen with both, rep-PCR and MALDI-TOF MS.
Conclusions: AmpC-producing P. mirabilis is an emergent pathogen. The high genetic variability detected suggests that the spread of the resistance mechanism is more probable than a clone dispersion. Automated rep-PCR and MALDI-TOF MS show as fast and decisive methods for bacterial strain typing in clinical microbiology laboratories.
  

 

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Rev Esp Quimioter 2012:25(4):252-255

Is it necessary to know which workers are carriers of MRSA in contact with cancer patients?                   

T. GARCÍA-LOZANO, A. EGIDO, E. CONTEL, M. I. PICÓN, M. A. MARTÍNEZ, E. AZNAR                                                                               

Our objective was to determine the prevalence of methicillin-resistant Staphylococcus aureus in workers who had direct contact with oncologic patients infected with MRSA and admitted to the intensive care unit of the Valencian Institute of Oncology. A study of prevalence of MRSA colonization of 62 workers was performed. Samples were taken from nose and pharynx in each of the workers. After 24 hours of incubation in Amies transport medium Viscose (Eurotubo®), 124 samples were seeded (N = 124) in chocolate agar agar, MRSA II and BHI broth (Brain Heart Infusion). Those colonies that were identified by Gram stain gram-positive cocci in clusters available, catalase positive and coagulase positive were processed for study of sensitivity by Kirby-Bauer method and screening test for methicillin (10μg of Oxoid®) on Mueller-Hinton (Becton-Dickinson®, BD), supplemented with NaCl (2%). Those confirmed MRSA isolates, he returned to perform sensitivity study by microdilution (MicroScan®, Siemens) to determine the MIC (mg/L). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was 1.61% (1) and 12.90% (8) for methicillin-sensitive Staphylococcus aureus (MSSA), from nostrils. The measures implemented were: nasal application of mupirocin to the worker colonized control isolation measures in infected patients and indoctrination of the personnel involved.  

 

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Rev Esp Quimioter 2012:25(2):129-133

Peripheral venous catheter-related bacteremia in a general hospital     

M. DELGADO-CAPEL, A. GABILLO, L. ELIAS, J. C. YÉBENES, G. SAUCA, J. A. CAPDEVILA                                                               

 
Introduction. Catheter sepsis is a constant and serious problem in our hospitals for the cost it generates, both in terms of morbidity and economics. It’s becoming more frequent also in peripherally inserted catheters. Our study aims to know the importance and characteristics of peripheral venous catheter bacteremia in a general hospital.
Material and methods. Prospective and comparative analysis of all episodes of central and peripheral venous catheter-related bacteraemia, in 2009.
Results. Twenty-eight episodes of catheter-related bacteraemia in a total of 25 patients. Sixteen episodes originated in central catheter (57.2%), 11 in peripheral (39.3%) and 1 in peripherally inserted central catheter (3.5%). Two cases of exitus directly related to the peripheral catheter infection. Etiology: 13 episodes of S. aureus (3 MRSA), including 8 in peripheral catheter (8/13, 61.5%), 12 episodes of plasma coagulase negative staphylococcus, including 2 in peripheral catheter (2/12, 16.6%).
Conclusions. Peripheral catheter-related bacteraemia is an emerging health problem with important clinical and prognostic connotations for patients. It is necessary continuous training on correct handling measures to prevent intravascular catheters infections including peripheral catheters in every hospital ward. 

 

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Rev Esp Quimioter 2012:25(4):256-260

Evaluation of the Sensititre Yeast One microdilution method for susceptibility testing of Candida species to anidulafungin, caspofungin, and micafungin                    

L. GARCÍA-AGUDO, P. GARCÍA-MARTOS, J. MARTOS-CAÑADAS, P. AZNAR-MARÍN, P. MARÍN-CASANOVA, M. RODRÍGUEZ-IGLESIAS                                                                                 


Introduction. Echinocandins represent a new antifungal group with potent activity against Candida species. The purpose of our study was to evaluate the utility of the Sensititre Yeast One method to determine the in vitro activity of anidulafungin, micafungin, and caspofungin against Candida species isolated from clinical specimens.
Methods. A total of 131 Candida strains were tested using Sensititre Yeast One colorimetric microdilution method. They belonged to the following species: 42 C. albicans, 36 C. glabrata, 21 C. parapsilosis, 12 C. tropicalis, 10 C. krusei, 3 C. guilliermondii, 2 C. famata, 3 C. kefyr, 1 C. lusitaniae, 1 C. zeylanoides, and 1 C. lipolytica. For being considered susceptible the strains had to be inhibited by concentrations ≤2 mg/L of anidulafungin, caspofungin or micafungin.
Results. The 80.1% of the strains tested were inhibited by concentrations ≤0.25 mg/L of anidulafungin and micafungin. The activity of caspofungin was slightly lower (78.6% of strains inhibited by concentrations ≤0.25 mg/L). The 96.9% of strains turned out susceptible to concentrations ≤2 mg/L against the three echinocandins. Two strains of C. parapsilosis (9.5%), one of C. guilliermondii, and two of C. famata showed non-susceptible to one or more echinocandins.
Conclusions. In our series, anidulafungin, micafungin, and caspofungin were effective against C. albicans, C. glabrata, C. tropicalis, C. krusei, C. kefyr, C. lusitaniae and C. lipolytica. The 96.9% of strains were susceptible to all three echinocandins. Thus, echinocandins are proved to exhibit excellent activity to the Candida species most frequently involved in human infections, except Candida parapsilosis.  

 

Rev Esp Quimioter 2012:25(4):256-260 [pdf]

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