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 2011:24(2):57-66

Bacteraemia due to Escherichia coli producing extended-spectrum betalactamases (ESBL): clinical relevance and today’s insights  

A. M. GARCÍA-HERNÁNDEZ, E. GARCÍA-VÁZQUEZ, A. HERNÁNDEZ-TORRES, J. RUIZ, G. YAGÜE, J. A. HERRERO, J. GÓMEZ     

 

Antibiotic resistance is an old problem with new face as the rate of infections due to multidrug resistant bacteria is higher everyday and the number of new antibiotics to overwhelm the problem is becoming smaller. E. coli is the most frequent agent causing nosocomial or community-acquired bacteraemia being in our country 10% of them extended-spectrum betalactamases (ESBL) producing E. coli isolates. Nowadays the number of community- acquired or health-related infections caused by these ESBL producing E. coli is increasing. CTX-M has also become the most frequent ESBL compared to other enzymes. The role of these enzymes as a virulence factor increasing mortality in patients with bacteraemia due to E. coli is not well defined. The relevance of ESBL-E. coli seems to be related with the higher frequency of inadequate treatment and therefore the importance of identifying factors or features that might predict that the patient’s infection is due to one of these isolates. In terms of prevention and control of infection measures, the role of patient’s isolation is not clear but a proper prescription of antibiotics and antibiotic control policies are probably important to reduce the problem.    

 
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Rev Esp Quimioter 2011:24(3):154-163

Pharmacoeconomic assessment of daptomycin as first-line therapy for bacteraemia and complicated skin and skin structure infections caused by gram-positive pathogens in Spain      


S. GRAU, P. REBOLLO, J. CUERVO, S. GIL-PARRADO            

Objective: To assess the efficiency of daptomycin as firstline therapy (D) versus daptomycin as salvage therapy after vancomycin (V→D ) or linezolid (L→D) failure in gram-positive bacteraemia and complicated skin and skin-structure infections (cSSTIs).
Methods: Cost-effectiveness analysis of 161 bacteraemia and 84 cSSTIs patients comparing the above mentioned therapeutic alternatives was performed using the data from 27 Spanish hospitals involved in the EUCORE study. Direct medical costs were considered. Patients were observed from the first antibiotic dose for infection until either the end of daptomycin therapy or exitus. A multivariate Monte Carlo probabilistic sensitivity analysis was applied for costs (lognormal distribution) and effectiveness (normal distribution).
Results: In terms of effectiveness there were no statistical differences between groups but referring total costs per patient, there were significant differences. Sensitivity analysis confirmed that D dominates over L→D between 44.2%-62.1% of simulations in bacteraemia and between 48.2%-67.5% in cSSTIs. In comparison to V→D, D dominance was detected in 29.2%-33.2% of simulations in bacteraemia and between 48.2%-59.3% in cSSTIs.
Conclusions: Daptomycin as first-line therapy dominates over daptomycin as salvage therapy after linezolid failure both in bacteraemia and cSSTIs. Comparing daptomycin as first-line therapy with its use after vancomycin failure, in cSSTIs the former is dominant. In bacteremia daptomycin as first line therapy is as effective as daptomycin as salvage therapy after vancomycin failure and implies lower costs. 

 
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Rev Esp Quimioter 2011:24(2):67-73

Pharmaecology  

J. GONZÁLEZ, A. ORERO, V. OLMO, D. MARTÍNEZ, J. PRIETO, J. A. BAHLSEN,  F. ZARAGOZÁ,  J. HONORATO       

 

Two of the main characteristics of western societies in the last fifty years have been the medicalization of the human life and the environmental degradation. The first one has forced human being to consider medicines use related to what would be rational, reasonable and well-reasoned. The second one brought us to a new ecologist conscience.
In relation to the “human social system”, the effects of medication can be considered very positive as a whole, particularly those related to the amazing increase of expectative and quality of life. But, along with those unquestionable beneficial effects, medicines have also caused some negative effects for other biotic and abiotic systems, such as microbian alterations and their undesirable consequences which have involved the massive use of antibiotics in medicine and veterinary, the uncontrolled elimination of millions of doses of all kind of drugs, additives and excipients, etc., as well as atmospheric contamination and degradation of forests and deep oceans which can have been caused by investigation and production of determinated drugs. In this context pharmaecology appears as a scientific discipline that studies the research (R), development (D), production (P), and utilization (U) of drugs and medical substances in relation to the environment. From a farmaecologic perspective the drugs utilization has its development in three main contexts, all of them closely related: prescription quality, farmaceutical care, and patient’s active participation in his own disease and treatment. 

 
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Rev Esp Quimioter 2011:24(4):175-183

Antimycobacterial natural products – an opportunity for the Colombian biodiversity       


J. BUENO, E. D. COY, E. STASHENKO            

It is estimated that one-third part of the world population is infected with the tubercle bacillus. While only a small percentage of infected individuals will develop clinical tuberculosis, each year there are approximately eight million new cases and two million deaths. Mycobacterium tuberculosis is thus responsible for more human mortality than any other single microbial species. The goals of tuberculosis control are focused to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug-resistance. For over 50 years, natural products have served us well on combating infectious bacteria and fungi. During the 20th century, microbial and plant secondary metabolites have helped to double our life span, reduced pain and suffering, and revolutionized medicine. Colombia is a megadiverse country with enormous potential to offer leads for new antimycobacterial drugs. The principal aim of this article is to show a state of the art on antimycobacterial natural products research in Colombia compared to the rest of the world, in order to develop programs for bioprospecting with a view to determining the biological activity for pharmaceutical and industrial application of natural products in our country. 

 
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Rev Esp Quimioter 2011:24(2):74-78

Activity of vancomycin, ciprofloxacin, daptomycin, and linezolid against coagulase-negative staphylococci bacteremia   

M. FAJARDO, R. HIDALGO, S. RODRÍGUEZ, F. F. RODRÍGUEZ-VIDIGAL, A. VERA, M. ROBLES       

 

Objective. Multiresistant coagulase-negative staphylococci (CNS) infections are mainly increased in hospitalized patients. We have studied the activity of vancomycin, ciprofloxacin, daptomycin and linezolid in methicillin-resistant CNS strains, isolated from true blood cultures.
Methods. We collected 87 strains of different CNS species from positive blood cultures. Staphylococci were identified by MicroScan Walkaway (Dade Behring, Siemens) and with the Api ID 32 Staph (BioMerieux, France). The susceptibility to oxacillin, vancomycin and ciprofloxacin was performed by automatic microdilution plate as cited above. The susceptibility to daptomycin and linezolid was performed by Etest (AB BioMerieux, Solna, Sweden). Interpretative criteria were done following the CLSI guidelines.
Results. Eighty-seven CNS strains were studied: 55 (63%) were S. epidermidis, 15 (17%) S. haemolyticus, 10 (12%) S. hominis, and 7 (8%) other species. Fifty-three (61%) strains showed loss of susceptibility to vancomycin, MIC = 2 mg/L. Ciprofloxacin resistance, MIC > 2 mg/L, was observed in 56 (64%) strains. Daptomycin resistance was not observed, with a susceptibility range between 0.032-1 mg/L and modal value of 0.25 mg/L. Ten strains (11.5%) resistant to linezolid were observed. Nine patients were in ICU, where the average length of stay was 38 days (range 16-58 days) and one belonged to Hepato-Pancreatic Surgery, where he stayed for 64 days.
Conclusions. Low susceptibility to vancomycin is frecuent in the CNS strains studied in our hospital. Daptomycin shows a high efficacy against CNS, and it could be useful for the treatment of primary bacteremia or catheter associated bacteremia. The massive and continuous use of linezolid has led to the appearance of resistance. 

 
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Rev Esp Quimioter 2011:24(4):184-190

Bacteroides mobilizable and conjugative genetic elements: antibiotic resistance among clinical isolates          


C. QUESADA-GÓMEZ              

The conjugation is one of the most important mechanisms of horizontal gene transfer in prokaryotes, leading to genetic variation within a species and the acquisition of new traits, such as antibiotic resistance. Bacteroides is an obligate anaerobe of the colon and a significant opportunistic pathogen. Antibiotic resistance among Bacteroides spp. is rapidly increasing, largely due to the dissemination of DNA transfer factors (plasmids and transposons) harbored by members of this genus. Transfer factors can be divided into two classes, conjugative and mobilizable. Species of the intestinal Bacteroides have yielded different resistance plasmids, all of which have been intensely studied, the plasmids encode high-level MLS resistance conferred by a conserved erm gene. It has been reported an interesting observation associated with the transfer of several of these types of elements, all of which conferred Tcr and displayed greatly increased transfer efficiency following exposure to tetracycline. Many of the conjugative transposons (CTns) in Bacteroides are related to various genetic elements (such as CTnDOT, CTnERL, NBU and others). CTnDOT carries a tetracycline resistance gene, tetQ, and an erythromycin resistance gene, ermF. Resistance to drugs used to treat Bacteroides infections, such as clindamycin, has also been increasing. These conjugal elements have been found in Bacteroides clinical isolates. Thus, horizontal gene transfer could conceivably have played a role in the rising incidence of resistance in this bacterial group. 

 
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Rev Esp Quimioter 2011:24(2):79-83

Do general practitioners follow the therapeutical recommendations of cystitis in women?. INURA study   

G.RABANAQUE, A. LÓPEZ, J. M. COTS, C. LLOR       

 

Objective: The management of lower urinary tract infections varies from physician to physician. The aim of this study was to assess whether general practitioners follow the evidence-based guidelines for the management of cystitis in women.
Methods: Cross-sectional study carried out from March to July 2009 in which physicians consecutively registered in a template during a 8-week period the first six episodes of cystitis by means attended at the medical consultation. Age, episode of infection, associated morbidity, antibiotic prescription, and type of antibiotic course (short or long regimen) were determined.
Results: Out of 176 physicians invited to participate, 110 included 658 women with lower urinary tract infections with antibiotic treatment being administered in 634 cases. Short courses were given to 385 women (60.7%) and 249 women were given long schedules (39.3%). A total of 343 out of all noncomplicated cystitis were treated with short courses (62.9%) and 75 out of complicated cystitis were treated with long courses (66.4%). First-choice antibiotics were administered as empiric treatment in only 111 women (17.5%).
Conclusions: These results highlight a poor adherence of general practitioners to current recommendations of clinical practice guidelines in cystitis with a low utilization of first-choice antibiotics. 

 
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Rev Esp Quimioter 2011:24(4):191-197

Outpatient use of topical antimicrobials in Spain associated with other drugs (2005-2007)          


P. MORI, D. MARTÍNEZ, J. BENEIT, E. PACHECO, J. GONZÁLEZ              

Introduction: The consumption of antibiotics for systemic use has been well studied. However, data of topical use in our country are an anecdotal reference in the literature.
Objective: To evaluate the outpatient use of topical antimicrobials in Spain associated with other drugs during the period December 2005 and November 2007.
Methods: A descriptive quantitative study was conducted between December 1, 2005 to November 30, 2007. The sample amounted to a total of 112 drugs, representing 131 dosage forms. The data on consumption of drugs were sold by the company Intercontinental Marketing Services (IMS), while demographic data were obtained from the municipal census of 2006 and 2007. The study variables were grouped into three categories: those relating to consumption, those on medications and other variables such as geographic location and time period.
Results: During the study period the outpatient consumption of topical antimicrobials in Spain was 41.755.951 vials (130.637.368 euros) whose composition included associations between antimicrobials or antimicrobials with other drugs. The average monthly consumption amounted to 1.739.831 vials and 5.443.223 euros. The dermal route of administration was the most dispensed and according to the Anatomical, Therapeutic, Chemical classification system (ATC) and the D07CC subgroup was the most used. The association between tobramycin and dexamethasone ophthalmic suspension as 30% was the drug most used in Spain.
Conclusions: The consumption of topical antimicrobials in Spain during the period 2006-2007 increased by 2.36% in the number of vials and 7.28% in economic cost. These antimicrobials were more used in summer. The average cost of a topical antimicrobial was half (3.13 euros) compared to the average cost of a drug (7.89 euros).group. 

 
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