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. 

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

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. 

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

Treatment of chronic hepatitis C virus infection. A study of best predictors for response          

N. OSPINA, J. L. RODRÍGUEZ, M. HERNÁNDEZ, C. GARCÍA, J. M. MARTÍN, E. REDONDO, L. OLIVIA, M. J. PENA              

Objective: The aim of this study was evaluate the rate of sustained viral response (SVR) and the influence of different factors on the SVR in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon alfa 2a and ribavirin.
Methods: We retrospectively analysed 272 naïve patients with chronic hepatitis C who had been treated for 24 weeks or 48 weeks and had been followed for an additional 6 months thereafter.
Results: Out of 272 patients, 243 completed the entire treatment. The overall SVR rate in intent-to-treat analysis was 66.5% and in treated patients was 74.5%. In an univariate analysis, the SVR was associated with age <40 years (84.4%), pre-treatment viral load <500.000 IU/ml (86.9%), non-1 genotype HCV (86.4%), non cirrhosis or pre-cirrhosis (76.5%), rapid virologic response (RVR) (91.4%) and early virologic response (EVR) (83.8%). In the multivariate logistic regression analysis, the presence of an infection caused by a non-1 genotype and to achieve ERV were independent predictors of SVR. The RVR and histological stage of liver disease were not included in the multivariate analysis because these data were not available in most of the patients. The PPV and NVP of RVR were 91.5% and 48.7% respectively, of EVR were 83.8% and 95.8% respectively and of complete EVR were 91.3% and 78.7%, respectively.
Conclusions: The SVR was higher than in other studies. The genotype and EVR were independent factors to predict the effect of antiviral therapy. The EVR had a high NPV and the complete EVR a high PPV. 

 
Rev Esp Quimioter 2011:24(4):198-203 [pdf]

Burkholderia cepacia bacteremia: a prospective analysis of 33 episodes          

M. IBARGUREN, N. COBOS-TRIGUEROS, Á. SORIANO, J. A. MARTÍNEZ, Y. ZBOROMYRSKA, M. ALMELA, J. MENSA              

Introduction: The aim of this study is to describe clinical characteristics and outcome of Burkholderia cepacia bacteraemia, susceptibility of the isolates and differences between cases from epidemic outbreaks and sporadic cases.
Material and methods: From 1993 to 2009, episodes of B. cepacia bacteraemia were prospectively collected in a university hospital.
Results: A total of 33 episodes were included, of which 21 were part of two outbreaks (9 in 1994 and 12 in 2006). Outbreak cases had a median age of 58 years, 45% had neoplasia, median length of stay until bacteraemia was 15 d (range 0-120) and 82% had received an antibiotic. The most prevalent sources of bacteraemia were catheter (48%) and unknown (33%). On the other hand, sporadic cases stayed longer until diagnosis (median 25 days versus 11, p=0.041) and showed a trend to have neoplasia more frequently (83% versus 33%, p=0.083). Susceptibility to antibiotics was varied and co-trimoxazole was the only active agent against all strains.
Conclusions: B. cepacia is an uncommon pathogen, which affects patients with prolonged hospitalization and severe comorbidities. The identification of more than one case in a short term of time should raise the suspicion of an outbreak. 

 
Rev Esp Quimioter 2011:24(4):209-211 [pdf]

Nosocomial infection following video-assisted thoracoscopic surgery           

D. N. NAN, M. FERNÁNDEZ-AYALA, C. FARIÑAS-ÁLVAREZ, R. MONS, J. GONZÁLEZ-MACÍAS, M. C. FARIÑAS                  

Objectives: To assess the incidence and risk factors for nosocomial infection after video-assisted thoracic surgery (VATS).
Methods: Prospective cohort study of all consecutive patients who underwent VATS surgery during 20 months. Patients were visited on a daily basis and followed up until they were discharged from the hospital
Results: During the study period 217 patients (70.1% men; mean age, 50.9 years, range 15-85 years) underwent VATS. Fourteen (6%) episodes of postoperative infection were diagnosed in 13 patients, including pneumonia (n = 2), lower respiratory tract infection (n = 9), surgical site infection (n = 2), and urinary tract infection (n = 1). Prior inmunosupresion (adjusted odds ratio [OR], 2.70; 95% confidence interval [CI], 1.52-4.84), prior infections (OR, 14.9; 95% CI 1.91-116.5), preoperative stay > 2 days (OR, 3.37; 95% CI 1.00-11.40), neoplasia (OR, 3.69; 95% CI, 1.94-7.06) duration of surgery > 45 minutes (OR, 5.91; 95% CI, 1.00-36.40) and presence of central venous catheter (OR, 16.40; 95% CI, 2.29-117.20), were independent risk factors for nosocomial infection.
Conclusions: Nosocomial infection rate after VATS was low. Respiratory infection was the most common infection. Factors which affect patient immunity, preoperative stay and perioperative-related variables were independently associated with infection. 

 
Rev Esp Quimioter 2011:24(4):217-222 [pdf]