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(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.

 

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

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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(3):183-188

Antimicrobial resistance of the most frequently isolated microorganisms in the Hospital General La Mancha Centro between June 2009 and May 2010                 

M. A. ASENCIO, R. CARRANZA, M. HUERTAS                                                                           

 
Introduction: During the last two decades an increased incidence of infections caused by multiresistant bacteria has been observed. The spread of these microorganisms in the hospital is a major therapeutic and epidemiological problem. The aim of this study was to determine local resistance patterns of microorganisms causative of multirresistant infections in patients admitted to our hospital.
Methods: A retrospective study was designed, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii strains isolated from clinical and surveillance samples of patients admitted to the Hospital General La Mancha Centro, between June 2009 and May 2010.
Results: The rate of S. aureus isolates resistant to oxacillin was 50%, with 0% resistance to vancomycin. The percentage of resistance to 3rd generation cephalosporins in E. coli and K. pneumoniae was 17 and 19%, respectively; the ESBL-production in enterobacterial strains was 15 and 19%, respectively, and the quinolone resistance was 41 and 28%, respectively. The resistance of P. aeruginosa to ceftazidime and imipenem was 30 and 40%, respectively. Most strains of A. baumannii studied came from a single multidrug-resistant clone, endemic in the ICU of our hospital.
Conclusions: Of particular concern is the high rate of MRSA, E. coli and K. pneumoniae ESBL producers and resistant to fluoroquinolones as well as P. aeruginosa multiresistant. A. baumannii isolates belong mainly to endemic multidrug-resistant clone from the ICU.

 

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Rev Esp Quimioter 2012:25(3):189-193


Evaluation of the variability in the susceptibility of Acinetobacter baumannii to tigecycline in the same medium with two methods of quantitative diffusion different commercial                 

R. TEJERO, M. CAUSSE, M. A. MORENO, F. SOLÍS, F. RODRÍGUEZ-LÓPEZ, M. CASAL                                                                           

 
Introduction: Tigecycline may be a therapeutic alternative for the control of multidrug-resistant Acinetobacter baumannii, although there is no consensus on the cutoffs or susceptibility to the variability of the minimum inhibitory concentration (MIC) according to the culture medium and strips for the antibiogram against this microorganism by quantitative diffusion method. Therefore, the objective was to verify this variability and propose epsilometer test strip that more closely resemble to the standard method.
Material and methods: 38 strains of A. baumannii were selected and evaluated their susceptibility to tigecycline with two different commercial strips (E-TEST and Liofilchem). MICs were compared with those obtained by the standard technique of microdilution broth.
Results: MICs obtained by the Liofilchem strip were more similar to standard method than those obtained by E-TEST strips.
Conclusion: In the two studied strips, higher MICs to those obtained by the standard method were observed leading to false-positive tigecicline resistance in many cases. However, the Liofilchem strip showed the results more closely resemble to the standard method.

 

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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 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 2012:25(3):206-215


Impact of liposomal amphotericin B on renal function in critically ill patients with renal function impairment                   

F. ÁLVAREZ-LERMA, M. C. SORIANO, M. RODRÍGUEZ, M. CATALÁN, A. M. LLORENTE, N. VIDART, M. GARITACELAYA, E. MARAVÍ, E. FERNÁNDEZ, F. ALVARADO, M. LÓPEZ, B. ÁLVAREZ-SÁNCHEZ, J. ESPINOSA, E. QUINTANA AND THE STUDY GROUP OF LIPOSOMAL AMPHOTERICIN B IN THE ICU                                                                          

 
Objetive: To assess the tolerability of liposomal amphotericin B (L-AmB) in critically ill patients with elevated serum creatinine concentrations (Cr) (> 1.5 mg/dL) at starting L-AmB therapy.
Methods: Retrospective, multicenter, comparative study of two cohorts of critically ill patients treated with L-AmB during 3 or more days, the difference between them was the level of Cr at the beginning of treatment. A cutoff value of Cr of 1.5 mg/dL was established. Patients undergoing extrarenal depuration procedures before or 48 hours after starting L-AmB were excluded. The primary endpoint was the difference between Cr values at the end of treatment as compared with Cr at starting L-AmB. Secondary endpoints were treatment-related withdrawals, need of extrarenal depuration techniques, and treatment-related severe adverse events. Demographic data, underlying illness, indication of L-AmB therapy, concomitant risk factors of nephrotoxicity, and vital status at ICU and hospital discharge were recorded.
Results: A total of 122 patients admitted to 26 ICUs (16 with Cr > 1.5 g/dL; 106 with normal Cr levels) were recruited. Main reasons for the use of L-AmB in both groups were the broad spectrum of the drug and the presence of hemodynamic instability. L-AmB was administered as first-line treatment in 68.8% of patients with elevated Cr and in 52.8% with normal Cr. The APACHE II score on ICU admission was 25 in patients with elevated Cr and 17 in those with normal Cr values (p < 0.001). Duration of treatment with L-AmB was 16 and 12 days in patients with elevate and normal Cr values, respectively, with a mean dose of 3.5 vs 3.9 mg/kg/day. The use of concomiImpact tant nephrotoxic drugs, mortality rate, and ICU and hospital length of stay were similar in both cohorts. In patients with renal function impairment at the initiation of L-AmB treatment, an absolute decrease of Cf-Ci of 1.08 mg/dL was observed (P < 0.001). A decrease of Cr levels to normal limits was observed in 50% of the patients; in 37.5% of patients there was a decrease but normal levels were not achieved, whereas a Cr increased occurred in only one (6.25%) patient. None of the patients required withdrawal of L-AmB or use of extrarenal depuration procedures. Treatment-related severe adverse events were not reported.
Conclusions: In critically ill patients with impaired renal function, the impact of L-AmB on renal function was minimal. L-AmB can be used for the treatment of fungal infections in critically ill patients independently of renal function at the initiation of treatment.

 

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Rev Esp Quimioter 2012:25(3):226-239

Consensus Document on vaccination against influenza in health care workers                   

J. J. PICAZO, L. M. ALONSO, J. ARÍSTEGUI, J. M. BAYAS, J. SANZ, P.  DEL AMO, J. L. COBOS, J. RODRÍGUEZ-SALAZAR, M. SÁNCHEZ-PASTOR, R. DE LA CÁMARA, J. CARRATALÁ, J. L. CAÑADA, J. GONZÁLEZ-DEL CASTILLO, P. ALDAZ, F. PÉREZ-ESCANILLA, J. BARBERÁN, A. RODRÍGUEZ, D. VIGIL-ESCRIBANO, J. ESPINOSA-ARRANZ, J. BLANQUER, F. GONZÁLEZ-ROMO                                                                          

 
Health care workers (HCW) are included each year among risk groups for vaccination against influenza. However, vaccination coverage among this group in our country is very low, not exceeding 25%. Convinced that one of the best tools to increase this coverage among professionals in our country are the scientific evidence, 19 scientific societies and associations professionals bringing together health professionals more directly related to influenza as an health problem, and the General Nursing Council, met to discuss and develop this consensus document in order to inform HCW about the appropriateness of their vaccination against influenza and the benefits that flow from it for themselves, for their patients and for the rest of the population. This recommendation is based on 3 pillars: argument of necessity, ethics and exemplary.

 

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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.

 

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

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