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.  

 

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

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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(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.  

 

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Rev Esp Quimioter 2012:25(4):261-265

Resistance of Bacteroides isolates recovered among clinical samples from a major Costa Rican hospital between 2000 and 2008 to ß-lactams, clindamycin, metronidazole, and chloramphenicol                     

E. CORDERO-LAURENT, C. RODRÍGUEZ, E. RODRÍGUEZ-CAVALLINI, M. M. GAMBOA-CORONADO, C. QUESADA-GÓMEZ                                                                                 

 

Objective. To assess the susceptibility of 100 isolates of Bacteroides spp. recovered in a major Costa Rican hospital between 2000 and 2008 to several ß-lactams, chloramphenicol, clindamycin and metronidazole.
Methods. Susceptibility to amoxicillin, amoxicillin with clavulanic acid, piperacillin, piperacillin with tazobactam, ticarcillin, ticarcillin with clavulanic acid, cefoxitin, cefotetan, imipenem, chloramphenicol, clindamycin, and metronidazole was determined with the ATB ANA® system. In addition, minimum inhibitory concentrations (MIC) of clindamycin and metronidazole were determined with the broth microdilution method because these drugs are the treatment of choice for anaerobic infections in Costa Rica. Reference strains ATCC® 25285 and ATCC® 29741 were employed as indicated.
Results. According to the ATB ANA® system, 93 isolates were resistant to at least one antibiotic. Resistance to b-lactams was common. By contrast, resistance to ß-lactams supplemented with ß-lactamase inhibitors was rare. All of the strains were inhibited by imipenem and chloramphenicol. By a broth microdilución test, resistance to clindamycin was 20%, with MIC ranging from 64 mg/L to 256 mg/L; all of the strains were susceptible to metronidazole.
Conclusions. The high MIC for clindamycin obtained for the majority of the resistant strains is highly suggestive of the presence of mechanisms of acquired resistance among the isolates, therefore surveillance studies are required to determine its efficacy. The low resistance to metronidazole observed underlines its value as a first-line drug. On the other hand, imipenem could be used to treat infections that do not respond well to metronidazole or clindamycin.  

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Rev Esp Quimioter 2012:25(4):266-268

Susceptibility to fluconazole of clinical interest yeasts: new breakpoints                     

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

 

Introduction. Recently, Pfaller et al (Drug Resist Update 2010; 13:180-95), have proposed new breakpoints for determining the in vitro susceptibility to fluconazole of Candida albicans, C. parapsilosis and C. tropicalis. The aim of this study was to establish the variations in sensitivity of these species applying these breakpoints, in relation to those of the Clinical and Laboratory Standards Institute (CLSI).
Methods. We analyzed 112 strains of Candida: 49 C. albicans, 40 C. parapsilosis and 23 C. tropicalis. Susceptibility to fluconazole was performed by the method Sensititre YeastOne. The breakpoints used to determine the minimum inhibitory concentration (MIC) were identified by CLSI and the ones proposed by Pfaller et al.
Results. According to the CLSI criteria, all isolates were susceptible to fluconazole. MIC50 and MIC90 were 0.5 mg/L and 2 mg/L for C. albicans and C. parapsilosis, 0.5 mg/L and 1 mg/L for C. tropicalis. With the new criteria, 109 (97%) strains were susceptible. Variations were seen in C. albicans, with 3 strains (6%) susceptible dose-dependent.
Conclusions. When applying the breakpoints recommended by Pfaller et al, and EUCAST, the number of fluconazole- susceptible strains decreased according to the CLSI criteria, especially C. albicans.  

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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.  

 

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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.  

 

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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(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 2013:26(1):1-5

Use of peripheral catheters: too much to learn                                 
 

J. A. CAPDEVILA               

Frequently incident complications due to the use of peripheral catheters are considered not relevant. However, recently multiple observational studies have demonstrated its role causing nosocomial bacteraemia. Guidelines about prevention of catheter-related infection are focused in central lines instead of peripheral ones. This approach causes an important lack of knowledge about the best manner to manipulate peripheral lines.
Risk factors related to the development of a peripheral phlebitis, its clinical relevance and doubts related to prevention are presented and discussed in this article. The main objective is to alert about the importance of peripheral catheters in the prevention of nosocomial infection.

Rev Esp Quimioter 2013:26(1):1-5 [pdf]

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