Macrolides and staphylococcal biofilms                

J. PARRA-RUIZ, C. VIDAILLAC, M. J. RYBAK                            

Medical device-associated infections represent a growing problem with limited or no therapeutic options beyond implant removal. Bacterial biofilm is the major and the final determinant of the poor prognosis of these difficult-to-treat infections. Due to the high antimicrobial resistance level of bacteria organized in biofilms, combination therapy is most often recommended, and macrolides may represent antibiotics of choice. Their anti-biofilm activity has been successfully used in-vitro and in-vivo against biofilm-associated infections caused by Pseudomonas aeruginosa and other Gram-negative bacilli. However there is only little data regarding their clinical interest against infections involving staphylococcal biofilms. Despite controversial reports, there is growing in-vitro and in-vivo evidences of anti-staphylococcal biofilm activity of macrolides that could represent a significant advance in the battle against implant-related infections. 

 
Rev Esp Quimioter 2012:25(1):10-16 [pdf]

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.  

Rev Esp Quimioter 2012:25(4):269-273 [pdf]

Pneumococcal bacteremia in adult patients at a hospital in Madrid: serotypes and susceptibility                 

M. CORREA, J. C. SANZ, C. DE LAS CUEVAS, A. GUIU, D. DOMINGO, T. ALARCÓN, M. LÓPEZ-BREA                                                                       

 
Introduction. The aim of this study is to describe the distribution of Streptococcus pneumoniae serotypes, its antimicrobial susceptibility profiles and the relation with vaccines in pneumococcal invasive strains isolated from blood cultures of adult patients.
Methods. All pneumococci isolated (67 strains) from blood cultures were serotyped by latex agglutination (Pneumotest latex) and Quellung reaction (Statens Serum Institut, Denmark). Antimicrobial susceptibility testing to penicillin (PEN), cefotaxime (CT), erythromycin (ERY) and levofloxacin (LEV) was performed by the E-test method (Biomèrieux, France).
Results. Among the 67 strains isolated, the most prevalent serotypes were 22F (11.9%) and 3 (11.9%), the second most frequent were 7F (7.5%) and 19A (7.5%). The coverage of the strains by the pneumococcal 7-valent conjugate vaccine (VNC7V), pneumococcal 13-valent conjugate vaccine (VNC13V) and pneumococcal 23-valent polysaccharide (VNP23V) were 16, 49 and 82%, respectively. Serotypes 22F and 3 were responsible for 14 of the 48 episodes of pneumonia with bacteremia (29.2%) and only 2 of the 19 episodes (10.5%) of bacteremia without pneumonia. According to the 2007 CLSI criteria, 12 strains (17.9%) were non-susceptible to penicillin. Eleven of this 12 strains (91.7%) were resistant to erythromycin, simultaneously.
Conclusions. The most common serotypes were 22F, 3, 7F y 19A. Three of them (3, 7F y 19A) are serotypes that are covered by the new VNC13V but not by VNC7V. Serotype 22F is a serotype emergent that is not covered by the VNC7V. The percentage of non-susceptibility to penicillin and resistance to erythromycin was comparable to the percentage reported in our country.

Rev Esp Quimioter 2012:25(2):155-160 [pdf]

Activity of vancomycin, teicoplanin and linezolid in methicillin resistant coagulase-negative Staphylococci isolates from paediatric blood cultures                

M. FAJARDO, R. HIDALGO, S. RODRÍGUEZ, C. GAONA, R. M. SÁNCHEZ, R. HERNÁNDEZ, E. MARTÍNEZ, J. L. CORDEROM. T. MARTÍNEZ-IZQUIERDO                             

Introduction. Coagulase-negative-Staphylococci (CNS) are the major cause of bacteraemia and sepsis in newborns. CNS methicillin resistance and its loss of sensitivity to glycopeptide antibiotics, make treatment significantly more difficult in positive cocci infections.
Objective. To study MIC vancomycin, teicoplanin and linezolid in different species of CNS methicillin resistant isolates from blood cultures from paediatric patients.
Methods. Clinically relevant CNS methicillin resistant isolates from paediatric blood cultures from different hospitalization wards were tested. The isolates were identified by biochemical tests by means in the Combo panels 31 of MicroScan (Dade Behring, Siemens). Resistance to oxacillin and susceptibility to vancomycin, teicoplanin and linezolid were tested by microdilution panels as cited above. We also tested teicoplanin and linezolid sensitivity using Etest.
Results. 50 methicillin resistant strains were isolated: 37 (74%) S. epidermidis, 7 (14%) S. hominis, 4 (8%) S. haemolyticus and 2 (4%) Staphylococcus spp. 26 strains were observed with reduced susceptibility to vancomycin MIC = 2 mg/L, (22 S. epidermidis, 2 S. haemolyticus and 2 Staphylococcus spp.) and 21 strains with loss of susceptibility to teicoplanin, MIC = 4-16 mg/L (20 S. epidermidis and 1 S. haemolyticus). No CNS linezolid resistant was found.
Conclusions. There is a linear correlation between increased vancomycin MIC and teicoplanin MIC. There is a statistically significant difference (p <0.001) in the MIC of teicoplanin in the vancomycin group = 2 mg/L with respect to the vancomycin group ≤ 1 mg/L. We also observed very low levels of linezolid MIC for all strains. 

 
Rev Esp Quimioter 2012:25(1):25-30 [pdf]

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.  

Rev Esp Quimioter 2012:25(4):283-292 [pdf]