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. 

 

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

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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.  

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

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Rev Esp Quimioter 2009:22(4):224-227

Colonial architecture and growth dynamics of Staphylococcus aureus resistant to methicillin

F. GÓMEZ-AGUDO, M. L. GÓMEZ-LUS, M. T. CORCUERA, L. ALOU, M. J. ALONSO, D. SEVILLANO, D. VAL, A. PALMEIRO, N. IGLESIAS, J. PRIETO

 

The aim of the study was to explore the structure and growth dynamics of Staphylococcus aureus resistant to methicillin (MRSA) colonies using semithin sections visualized by light microscope. One S. aureus susceptible to methicillin (MSSA) and one MRSA clinical strains were studied. Colonies in agar plates were embedded in epoxy resin after each incubation period (24 h and 48 h) at 37ºC. Semithin sections of 0.5µm were stained with toluidine blue and visualized by light microscope. Microscopically, no structural differences were observed between SASM and SARM colonies but differences were observed in both strains between 24 and 48 h incubation periods. Colonies showed two layers clearly differentiated at24 h independently of the resistance to methicillin: (A) one basal layer with high density of population in contact with culture media, and (B) one superficial layer with a lower density of population. Colonies showed four layers at 48 h:(A) one basal layer with high density of population; (B) one clear layer constituted by very degraded bacterial remains in which can be observed cocci dispersed with their dyeing properties; (C) one mixed layer constituted by viable bacteria and little degraded bacterial remains (D) one superficial layer with a lower density of population than basal layer. Colonial architecture is a complex and time-dependent process.

 
Rev Esp Quimioter 2009:22(4):224-227 [pdf]

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Rev Esp Quimioter 2010:23(3):109-114

Treatment of human infections caused by Bartonella spp. 

L. PÉREZ-MARTÍNEZ, J. R. BLANCO, J. A. OTEO 

 

Infections by Bartonella spp. include a wide spectrum of emerging and re-emerging infectious diseases.There is not a universal therapy for this infection, therefore treatment should be chosen individually. The aim of this review is to update the therapeutics aspects of this kind of infections.

 
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Rev Esp Quimioter 2011:24(1):25-31

Predictive factors of 2009 H1N1 virus infection in patients with influenza syndrome

A. SUPERVÍA, F. DEL BAÑO, G. MALDONADO, O. PALLÀS, A. AGUIRRE, C. VILAPLANA, J. P. HORCAJADA, M. T. MARTÍNEZ-IZQUIERDO    

 

Introduction: Polymerase chain reaction (PCR) testing isone of the better techniques for viral detection in nasopharyngeal swabs. The objective of this study was to assess the percentage of positive swabs and to determine whether there were differences according to PCR positivity.
Material and Methods: A retrospective study of 362 patients with flu syndrome attended at the Emergency Department between July 15 and December 15, 2009, in whom PCR of nasopharyngeal swabs for the detection of H1N1 2009 influenza virus was performed.  Those cases in which swab testing was adequately requested were identified, and patients were divided into two groups according to positive or negative results for H1N1 2009 influenza virus.
Results: Nasopharyngeal swab was inadequately ordered in 87. In the remaining 275 patients, PCR was positive in 141. Patients with positive nasopharyngeal swabs were younger (mean [SD] age 36.1 [15] vs42.3 [18] years, P= 0.002), had lower white blood cell, neutrophil and lymphocyte counts, lower serum concentrations of C-reactive protein (5.15 [5] vs 10.5[12] mg/dL, P= 0.036) and lower incidence of radiological infiltrates (20.5% vs 33%, P= 0.036). In the logistic regression analysis, age, serum C-reactive protein levels, and lymphocyte count were independently associated with a positive nasopharyngeal swab.
Conclusions: About 50% of patients with flu syndrome had positive nasopharyngeal swabs for H1N1 2009 influenza virus. Age, C-reactive protein, and lymphocyte count were independent predictors of positivity.    


Rev Esp Quimioter 2011:24(1):25-31 [pdf]

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Rev Esp Quimioter 2011:24(3):131-135

Rapid identification and susceptibility testing of Gram-positive cocci in BacT/ALERT blood cultures by direct inoculation into the Vitek 2 system       

A. BARREALES, M. LARA, I. HERNÁNDEZ, Ó. DÍEZ           

 

Introduction: To provide the clinician with early information about blood culture results allows a better prognosis and a reduced mortality rate of the patient with sepsis. In order to contribute to this aim, we performed a study for the identification and susceptibility profiling of positive blood cultures by direct inoculation into the automated Vitek 2 system.
Materials and Methods: Blood cultures of 57 patients with monomicrobial bacteriaemia due to gram-positive cocci
were evaluated. Addition of saponin to the fluid from blood culture bottles was performed prior to the inoculation of Vitek 2 system cards. The same samples were also examined with the standard method starting from agar plate grown subcultures.
Results: Comparison between the results obtained with the standard method and the direct method revealed that 82% of the samples were correctly identified and that 97% of the isolates showed a concordant antimicrobial susceptibility profile for all drugs tested. Compared to the standard method, the very major error rate of the direct method was just 0.5%, the major error rate was 0.5%, and the minor error rate was 2%.
Conclusion: These data suggest that addition of saponin to the fluid from blood culture bottles of the BacT/ALERT® 3D before inoculation of the appropriate Vitek 2 cards leads to the rapid and reliable identification and susceptibility profiling of gram-positive cocci in blood samples. Compared to the standard method, the direct method would reduce turnaround time by at least 24 hours.

 
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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.  

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

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Rev Esp Quimioter 2010:23(3):115-121

Endotoxin adsortion as adjuvant therapy in gramnegative severe sepsis 

F.J. CANDEL, F. MARTÍNEZ-SAGASTI, M. BORGES, E. MASEDA, M. HERRERA-GUTIÉRREZ, J. GARNACHO-MONTERO, F.J. MAYNAR, R. ZARAGOZA, J. MENSA, J.R. AZANZA 

 

The mortality rate of severe sepsis and septic shock remains still high. Within the last years a better knowledge of its physiopathology and the implementation of a group of measures addressed to a fast identification and early treatment of the septic patients have proved to reduce mortality rate. Likewise, it continues being investigated in modulating the inflammatory response and limiting the harmful action of the bacterial products on the immune system. As a result of this research some endotoxin adsorber devices have been designed to control one of the most important targets that start the inflammatory cascade when gramnegative microorganisms are involved.The usefulness that these endotoxin removal devices might have as adjuvant treatment in the Septic Syndrome and its applicability are reviewed in this paper. Likewise a profile of patient that might be to the benefit of this therapy is suggested according to the current knowledge.  

 
Rev Esp Quimioter 2010:23(3):115-121 [pdf]

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