Rev Esp Quimioter 2012:25(2):134-138

Rifampin breakpoint for Acinetobacter baumannii based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation     

J. A LEPE, E. GARCÍA-CABRERA, M.V. GIL-NAVARRO, J. AZNAR                                                                

 
Objective: The aim of this study is to develop a pharmacokinetic–pharmacodynamic (PK–PD) rifampin breakpoint for Acinetobacter baumannii based on Monte Carlo simulation and to compare it with the reference value establish by the French Society for Microbiology (SFM).
Methods: A 10,000 subject’s Monte Carlo simulation for rifampin with intravenous dose of 10 mg/Kg/day and 20 mg/Kg/day was performed. The distribution of MIC was calculated using unique clinical isolates of A. baumannii. The PK–PD parameter calculated was Cmaxfree/MIC.
Results: The isolates rifampin MIC50 and MIC90 were 2 and 32 mg/L respectively, ranging between 0.023-32 mg/L. According to interpretive criteria established by the SFM: 468 (75.8%) isolates were susceptible (MIC ≤ 4 mg/L) and 150 (24.2%) were non susceptible (MIC > 4 mg/L).
For 10 mg/Kg/day dose: the probability (%) of attaining Cmaxfree/ MIC ratio values = 8 by Monte Carlo simulation in the study population was 0.4%, the rifampin MIC cut off value obtained from an optimal treatment (target ≥ 90%), was 0.125 mg/L. The probability of obtaining a Cmaxfree/MIC ratio equal to 10 was 0.2% and the MIC cut off value obtained <0.125 mg/L.
At doses of 20 mg/kg/day: the probability of obtaining a Cmaxfree/MIC ratio equal to 8 was 0.8%, the rifampin MIC cut off value obtained was 0.25 mg/L. For a Cmaxfree/MIC = 10, it was 0.6% and 0.125 mg/L, respectively. The percentage of susceptible isolates ranging 0% to 1%, depending on the dose and therapeutic target used.
Conclusion: the rifampin breakpoints obtained from our PK/PD Monte Carlo simulation differ from those established by SFM, although further clinical studies in patients are needed to confirm our findings and improve the use of this antibiotic. 

 

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Rev Esp Quimioter 2012:25(4):261-265

Resistance of Bacteroides isolates recovered among clinical samples from a major Costa Rican hospital between 2000 and 2008 to ß-lactams, clindamycin, metronidazole, and chloramphenicol                     

E. CORDERO-LAURENT, C. RODRÍGUEZ, E. RODRÍGUEZ-CAVALLINI, M. M. GAMBOA-CORONADO, C. QUESADA-GÓMEZ                                                                                 

 

Objective. To assess the susceptibility of 100 isolates of Bacteroides spp. recovered in a major Costa Rican hospital between 2000 and 2008 to several ß-lactams, chloramphenicol, clindamycin and metronidazole.
Methods. Susceptibility to amoxicillin, amoxicillin with clavulanic acid, piperacillin, piperacillin with tazobactam, ticarcillin, ticarcillin with clavulanic acid, cefoxitin, cefotetan, imipenem, chloramphenicol, clindamycin, and metronidazole was determined with the ATB ANA® system. In addition, minimum inhibitory concentrations (MIC) of clindamycin and metronidazole were determined with the broth microdilution method because these drugs are the treatment of choice for anaerobic infections in Costa Rica. Reference strains ATCC® 25285 and ATCC® 29741 were employed as indicated.
Results. According to the ATB ANA® system, 93 isolates were resistant to at least one antibiotic. Resistance to b-lactams was common. By contrast, resistance to ß-lactams supplemented with ß-lactamase inhibitors was rare. All of the strains were inhibited by imipenem and chloramphenicol. By a broth microdilución test, resistance to clindamycin was 20%, with MIC ranging from 64 mg/L to 256 mg/L; all of the strains were susceptible to metronidazole.
Conclusions. The high MIC for clindamycin obtained for the majority of the resistant strains is highly suggestive of the presence of mechanisms of acquired resistance among the isolates, therefore surveillance studies are required to determine its efficacy. The low resistance to metronidazole observed underlines its value as a first-line drug. On the other hand, imipenem could be used to treat infections that do not respond well to metronidazole or clindamycin.  

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Rev Esp Quimioter 2012:25(1):4-9

Invasive fungal infection in critically ill patient: role of micafungin                

M. NIETO, E. ESCUDERO                         

The invasive fungal infections (IFIs) have increased in critically ill patients in recent years and are a serious complication that determine the evolution and prognosis of critically ill patients, especially invasive candidiasis (IC) and candidemia. Fortunately, treatment options for these infections have increased and there is a large arsenal of antifungal agents. This review of the literature, using PubMed and Cochrane databases, assesses the situation of the IFIs in critically ill patients and discusses the role of micafungin in this context. The broader spectrum of this candin, which gets the antifungal effect with lower MICs and that translates into greater clinical efficacy with a lower rate of adverse effects and easier to use, with proven cost-effectiveness compared with other antifungal, position micafungin as a useful therapeutic option for the management of invasive candidiasis / candidemia in critically ill patients. 

 
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Rev Esp Quimioter 2012:25(2):139-146

Antibiotic prescribing to the paediatric population of Castilla y León in the last decade: trends, seasonal fluctuations and geographical differences            

M. E. VÁZQUEZ, J. M. EIROS, F. MARTÍN, S. GARCÍA, R. M. BACHILLER, M. J. VÁZQUEZ                                                                   

 
Introduction. The development of antibiotic resistance is a danger to the health of the population, especially for children, due to low antimicrobial arsenal available to them.
Material and methods. We performed a retrospective observational study referred to the prescriptions of systemic antibiotic in the paediatric population of Castilla y León in the years 2001 to 2010.
Results. The total use of antibiotics outside hospitals is around to 20.7 DID (defined daily dose per 1,000 inhabitants per day). There are two different phases: the first from 2001 to 2007 where there is an increase of consumption, with a peak of 25 DID in 2003, following a phase of decline, with a minimum of 18 DID in 2010. Broad-spectrum penicillins are the most used. We also observe changes in prescription trends. It has a clear seasonal prescription profile related to acute respiratory infections (ARI) of winter, stands in February. The use of antibiotics varies substantially between different Health Areas.
Conclusions. We observed a decrease in antibiotic prescription to children in the last three years. Changes in the prescription profile for amoxicillin and at the expense of greater spectrum antibacterial antibiotics indicate a better match to therapeutic guidelines in recent years. The variability found in different Health Areas suggests the need for improvement in the rational use of antibiotic, at least to some.
 

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Rev Esp Quimioter 2012:25(4):266-268

Susceptibility to fluconazole of clinical interest yeasts: new breakpoints                     

L. GARCÍA-AGUDO, P. GARCÍA-MARTOS, P. MARÍN-CASANOVA, M. RODRÍGUEZ-IGLESIAS                                                                                   

 

Introduction. Recently, Pfaller et al (Drug Resist Update 2010; 13:180-95), have proposed new breakpoints for determining the in vitro susceptibility to fluconazole of Candida albicans, C. parapsilosis and C. tropicalis. The aim of this study was to establish the variations in sensitivity of these species applying these breakpoints, in relation to those of the Clinical and Laboratory Standards Institute (CLSI).
Methods. We analyzed 112 strains of Candida: 49 C. albicans, 40 C. parapsilosis and 23 C. tropicalis. Susceptibility to fluconazole was performed by the method Sensititre YeastOne. The breakpoints used to determine the minimum inhibitory concentration (MIC) were identified by CLSI and the ones proposed by Pfaller et al.
Results. According to the CLSI criteria, all isolates were susceptible to fluconazole. MIC50 and MIC90 were 0.5 mg/L and 2 mg/L for C. albicans and C. parapsilosis, 0.5 mg/L and 1 mg/L for C. tropicalis. With the new criteria, 109 (97%) strains were susceptible. Variations were seen in C. albicans, with 3 strains (6%) susceptible dose-dependent.
Conclusions. When applying the breakpoints recommended by Pfaller et al, and EUCAST, the number of fluconazole- susceptible strains decreased according to the CLSI criteria, especially C. albicans.  

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

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. 

 
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Rev Esp Quimioter 2012:25(2):147-154

Prospective comparison of severity scores for predicting mortality in community-acquired pneumonia              

S. LUQUE, J. GEA, P. SABALLS, O. FERRÁNDEZ, N. BERENGUER, S. GRAU                                                                      

 
Introduction. Specific prognostic models for communityacquired pneumonia (CAP) to guide treatment decisions have been developed, such us the Pneumonia Severity Index (PSI) and the Confusion, Urea nitrogen, Respiratory rate, Blood pressure and age ≥ 65 years index (CURB-65). Additionally, general models are available such as the Mortality Probability Model (MPM-II). So far, which score performs better in CAP remains controversial. The objective was to compare PSI and CURB-65 and the general model, MPM-II, for predicting 30-day mortality in patients admitted with CAP.
Methods. Prospective observational study including all consecutive patients hospitalised with a confirmed diagnosis of CAP and treated according to the hospital guidelines. Comparison of the overall discriminatory power of the models was performed by calculating the area under a receiver operator characteristic curve (AUC ROC curve) and calibration through the Goodness-of-fit test.
Results. One hundred and fifty two patients were included (mean age 73.0 years; 69.1% male; 75.0% with more than one comorbid condition). Seventy-five percent of the patients were classified as high-risk subjects according to the PSI, versus 61.2% according to the CURB-65. The 30-day mortality rate was 11.8%. All three scores obtained acceptable and similar values of the AUCs of the ROC curve for predicting mortality. Despite all rules showed good calibration, this seemed to be better for CURB-65. CURB-65 also revealed the highest positive likelihood ratio.
Conclusions. CURB-65 performs similar to PSI or MPMII for predicting 30-day mortality in patients with CAP. Consequently, this simple model can be regarded as a valid alternative to the more complex rules.

 

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

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.  

 

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Rev Esp Quimioter 2012:25(1):17-24

Liposomal amphotericin B: a unique pharmacokinetic profile. An unfinished story                

J. R. AZANZA, J. BARBERÁN                            

La anfotericina B en su formulación liposómica continúa siendo un fármaco de referencia en el tratamiento de las infecciones fúngicas sistémicas a pesar del tiempo transcurrido desde que se desarrolló. La ausencia de resistencias de los hongos, la farmacocinética, y el mejor perfil de tolerabilidad en relación con el resto formulaciones de anfotericina B, son motivos suficientes para justificar su protagonismo, El liposoma que contiene la anfotericina B liposómica es muy estable en relación con la presencia de colesterol y los fosfolípidos no presentan termolabilidad, por ello la anfotericina B apenas está presente en forma libre (<1%) lo que explica la baja incidencia de efectos relacionados con la administración y la reducción de la incidencia de nefrotoxicidad (mitad que con la anfotericina B complejo lipidico) y que incluso en algún estudio a dosis de 1 mg/kg se ha mostrado inexistente.Este perfil justifica concentraciones plasmáticas muy elevadas y un volumen de distribución y aclaramiento reducidos, con una semivida de eliminación muy prolongada. Existen evidencias que señalan que el liposoma a través de la anfotericina B es capaz de fijarse al ergosterol presente en membrana de hongo y sólo en ese momento se produciría la liberación del antifúngico que ejercería su efecto farmacológico.

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

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.

 

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