Rev Esp Quimioter 2012:25(1):42-46

Phenotypes and mechanisms of resistance to macrolides and lincosamides in Streptococcus agalactiae isolates with clinical significance in an eight-year period (2002-2010)                

F. ARTILES, A. CAÑAS, I. ÁLAMO, B. LAFARGA                               

 

Introduction. Streptococcus agalactiae is the most prevalent agent of invasive disease in the newborn (sepsis, pneumonia, and meningitis), as well as an important cause of puerperal fever, urinary tract infection and surgical site infection. The aim of our study was to know the evolution of macrolide and lincosamide resistance in this microorganism.
Methods. Resistance phenotypes were established according to the erythromycin-clindamycin induction test: M (efflux pump) or MLSB (methylase). Genetic mechanisms were detected by PCR for the following genes: ermB, ermA, ermTR, and mefA/E. Molecular typing was based on chromosomal DNA macrorestriction and detection of fragments using pulsed-field gel electrophoresis.
Results. During 8 years, 300 isolates of S. agalactiae were recovered. Seventy-eight (26%) were resistant to macrolides, and seventy (23%) were resistant to lincosamides. Constitutive MLSB was observed in 21% of the isolates (all but one carrying the ermB gene), with a erythromycin MIC90 ≥ 256 mg/L. Inducible MLSB was observed in 2.3% of the isolates (all carrying the ermTR gene), with a MIC90 of 6 mg/L. M phenotype was observed in 2.7% of the isolates (all carrying the mefA/E gene), with a MIC90 of 6 mg/L. Molecular typing revealed the presence of two major clones (A and B) comprising 56.6% of the isolates. Most of the isolates (90.5%) belonging to clon A carried the ermB gene.
Conclusions. Macrolide resistance in our area is similar to that observed in the rest of Spain, but there has been no increase in the incidence rate along the study period. 

 
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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.

 

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

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Rev Esp Quimioter 2012:25(1):47-55


Effect of protein binding on the activity of voriconazole alone or combined with anidulafungin against Aspergillus spp. using a time-kill methodology                

F. CAFINI, D. SEVILLANO, L. ALOU, F. GÓMEZ-AGUADO, M. T. CORCUERA, N. GONZÁLEZ, J. GUINEA, J. PRIETO                                                         

 

Objectives: the aims of the study were to explore the activity of total and free (according to protein binding) maximal concentrations achieved in serum after multiple doses of voriconazole 400/200 mg and anidulafungin 200/100 mg against Aspergillus fumigatus and Aspergillus flavus and the human albumin or serum effects on antifungal activity.
Material and methods: Time-kill curves were performed with two A. fumigatus and two A. flavus strains at voriconazole and anidulafungin Cmax concentrations using different media: a) RPMI broth (Cmax-RPMI); b) RPMI with human serum (Cmax-HS), and c) RPMI with human albumin (Cmax-HAlb). In parallel, free-drug (fCmax) concentrations considering theoretical protein binding were performed in RPMI broth. Aspergillus metabolic activity was measured by the XTT reduction assay.
Results: Voriconazol or voriconazole plus anidulafungin reduced >88.4% the metabolic activity of Aspergillus sp. at Cmax-RPMI and fCmax after 48 h of exposition. Anidulafungin alone showed poor metabolic reductions (<80.1% at Cmax-RPMI and <15% at fCmax). Anidulafungin activity, but not voriconazole activity alone or combined decreased in presence of HS or HAlb (more pronounced in A. flavus strains and HAlb). However, anidulafungin Cmax-HS or Cmax-HAlb against A. fumigatus strains were significantly more active (p<0.05) than fCmax in RPMI. These species and culture medium-dependent impact of human protein binding in the activity of anidulafungin was related to macroscopic and microscopic differences among mycelial mat grown in RPMI, HS or HAlb in whose XTT retention was different.
Conclusions: Synergism could not be demonstrated due to the high activity showed by voriconazole. Protein binding has not impact on voriconazole activity and this impact is considerably less than predicted by free concentration extrapolated from theoretical binding rate on anidulafungin. The XTT colorimetric assay needs to be standardized for use with Aspergillus spp. since without DMSO extraction the activity of echinocandins in a free-human protein RPMI medium could be overestimated. 

 
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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(1):56-64


Clinical characteristics and outcome of patients with pandemic 2009 Influenza A(H1N1)v virus infection admitted to hospitals with different levels of health-care 
                

M. GUTIÉRREZ-CUADRA, J.L. GONZÁLEZ-FERNÁNDEZ, P. RODRÍGUEZ-CUNDIN, C. FARIÑAS-ÁLVAREZ, M. V. SAN JUAN, J. A. PARRA, M. CARRASCOSA, M. C. FARIÑAS                                                         

Background. The outcome of patients with influenza A 2009 (H1N1)v virus infection taking into account hospital type has not been elucidated.
Objectives. To compare risk factors, clinical features and outcome of patients admitted to 3 public hospitals with different levels of health-care.
Methods: Prospective study of all non-pregnant adult patients admitted to 3 hospitals with pandemic H1N1 infection, from June 1 to December 31 and followed up until 1 month after discharge.
Results. During the study period, 111 patients with a mean age of 49 years (15-89) were hospitalized: 52 in hospital 1 (900-bed tertiary-teaching-hospital), 33 in hospital 2 (315-beds secondary-hospital) and 26 in hospital 3 (150-beds primary-care-hospital).Overall 80% of patients had at least 1 comorbid condition with no differences between hospitals. Symptoms or signs on admission were similar except for cough (P=0.01) more frequent in patients in hospital 1 and dyspnea (P=0.05), myalgia, arthralgia (P=0.04) and hypoxemia (P=0.009) present in more patients in hospital 2. In-hospital mortality rates were not statistically different between hospitals. In the stepwise analysis, independent predictors of mortality were pneumonia on admission (adjusted OR=8.68, 95%CI 1.0-82.43) and cardiac complications during hospitalization (adjusted OR=13.2, 95%CI 1.67-103.98).
Conclusions. Mortality of patients with pandemic H1N1 infection was influenced by patients underlying conditions, severity of disease (pneumonia) on admission and complications during hospitalization. Hospital-characteristics do not appear to have influenced severe outcome.. 

 
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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(1):65-73


Analysis of treatments used in infections caused by Gram-positive multiresistant cocci in critically ill patients admitted to the ICU 
                

F. ÁLVAREZ-LERMA, M. PALOMAR, P. OLAECHEA, J. INSAUSTI, M. J. LÓPEZ, M. P. GRACIA, R. GIMENO, I. SEIJAS                                                          

The appearance of new antimicrobials with activity against Gram-positive multiresistant cocci and knowledge of the limitations of glycopeptides has represented an important change in the use of these antibiotics.
Objetive. To analyze at the national level changes in the use of antibiotics with specific activity against Gram-positive multiresistant cocci in critically ill patients admitted to the ICU as well as the characteristics of patients treated with these agents and the forms of administration.
Material and methods. Retrospective cohort study of patients admitted to the ICU for more than 24 hours between 2008 and 2010 in the ENVIN-HELICS national registry. Cases were defined as patients who had received one or more of the following antibiotics: vancomycin, teicoplanin, linezolid or daptomycin. The characteristics of patients who used one or more of these agents were compared with those treated with other antibiotics. Indications and forms of use of each antibiotic were assessed. Descriptive results are presented.
Results. A total of 45,757 patients, 27,982 (61.2%) of whom received 63,823 antimicrobials were included in the study. In 6,368 (13.9%) patients, one or more antibiotics specifically active against Gram-positive multiresistant cocci were given. There was a predominance of the use of vancomycin and linezolid and an important increase in the prescription of daptomycin (+320%) and linezolid (+22.4%). In more than 95% of cases, linezolid and daptomycin were prescribed for the treatment of infections, whereas vancomycin and teicoplanin were used for prophylaxis in 20-25% of cases. Between 75% and 80% of indications for treating infections, antibiotics were used empirically except for daptomycin which was used as a directed treatment in 43% of the cases. Only in one third of the indications for empirical treatment, susceptible microorganisms were identified (appropriate treatment).
Conclusions. The use of antibiotics with activity against Gram-positive multiresistant cocci remained stable around 14% of all indications. The use of vancomycin and linezolid predominated and there was a clear trend towards an increase in the use of daptomycin and linezolid and a decrease in the use of glycopeptides. Empirical treatments were considered appropriate in only one third of cases.
  

 
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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(1):79-88


Prevention of perinatal group B Streptococcal disease. Updated Spanish recommendations 
                

J. I. ALÓS, A. ANDREU, L. ARRIBAS, L. CABERO, M. CUETO, J. LÓPEZ, J. C. MELCHOR, A. PUERTAS, M. DE LA ROSA, S. SALCEDO, M. SÁNCHEZ, M. J. SÁNCHEZ, R. TORREJÓN                                                          

It has been a significant reduction in neonatal group B streptococcus (GBS) infection in Spain following the widespread application of intrapartum antibiotic prophylaxis. In 2010, new recommendations have been published by the CDC and this fact, together with the new knowledge and experience available, has driven to the participating scientific societies publishing these new recommendations. In these recommendations is advised to study all pregnant women at 35-37 gestation weeks` to determine if they are colonized by GBS and to administer intrapartum antibiotic prophylaxis (IAP) to all colonized mothers. Microbiological methods to identify pregnant GBS carriers are updated and intrapartrum antibiotic prophylaxis in preterm labour and premature rupture of membranes and the management of the newborn in relation to GBS carrier status of the mother are also revised.
  

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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.

 

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

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