Rev Esp Quimioter 2012:25(4):256-260

Evaluation of the Sensititre Yeast One microdilution method for susceptibility testing of Candida species to anidulafungin, caspofungin, and micafungin                    

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


Introduction. Echinocandins represent a new antifungal group with potent activity against Candida species. The purpose of our study was to evaluate the utility of the Sensititre Yeast One method to determine the in vitro activity of anidulafungin, micafungin, and caspofungin against Candida species isolated from clinical specimens.
Methods. A total of 131 Candida strains were tested using Sensititre Yeast One colorimetric microdilution method. They belonged to the following species: 42 C. albicans, 36 C. glabrata, 21 C. parapsilosis, 12 C. tropicalis, 10 C. krusei, 3 C. guilliermondii, 2 C. famata, 3 C. kefyr, 1 C. lusitaniae, 1 C. zeylanoides, and 1 C. lipolytica. For being considered susceptible the strains had to be inhibited by concentrations ≤2 mg/L of anidulafungin, caspofungin or micafungin.
Results. The 80.1% of the strains tested were inhibited by concentrations ≤0.25 mg/L of anidulafungin and micafungin. The activity of caspofungin was slightly lower (78.6% of strains inhibited by concentrations ≤0.25 mg/L). The 96.9% of strains turned out susceptible to concentrations ≤2 mg/L against the three echinocandins. Two strains of C. parapsilosis (9.5%), one of C. guilliermondii, and two of C. famata showed non-susceptible to one or more echinocandins.
Conclusions. In our series, anidulafungin, micafungin, and caspofungin were effective against C. albicans, C. glabrata, C. tropicalis, C. krusei, C. kefyr, C. lusitaniae and C. lipolytica. The 96.9% of strains were susceptible to all three echinocandins. Thus, echinocandins are proved to exhibit excellent activity to the Candida species most frequently involved in human infections, except Candida parapsilosis.  

 

Rev Esp Quimioter 2012:25(4):256-260 [pdf]

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Rev Esp Quimioter 2010:23(2):93-99

Epidemiology and clinical presentation of Panton-Valentin leukocidin positive methicillin-resistant Staphylococcus aureus

N. COBOS-TRIGUEROS, C. PITART, F. MARCO, J. A. MARTÍNEZ, M. ALMELA, J. LÓPEZ, M. ORTEGA, A. SORIANO, J. MENSA 

 

Introduction: the aim of our study was to review the epidemiology and clinical manifestations of infections due to Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (PVL-MRSA).
Material and methods: Medical history of patients infected by MRSA-PVL admitted to our hospital from January 2007 to July 2009 was reviewed. PVL and the type of cromosomic cassette were determined in all strains by PCR.
Results: A total of 37 cases were included. Seventy percent were males and the median age was 39 years. Sixtytwo percent were Spanish, 14 (37.8%) were HIV-positive and 11 (29.7%) were homosexual. The source of the infection was the skin and soft tissue in 36 cases and pneumonia in 1. Sixteen patients were hospitalized, 5 had bacteremia and 5 developed septic metastasis. The relapse rate was 24% (9 cases). The prevalence during the study period was 11.2% of all MRSA isolated (37 out of 329). All the strains had a cromosomic cassette type IV and were susceptible to cotrimoxazole, rifampin, vancomyin, daptomycin and linezolid. The MIC of vancomycin, measured by E-test, was ≥1.5 mg/L in 28 out of 34 cases (82.3%).
Conclusions: Eleven percent of the MRSA strains isolated in our hospital are PVL positive. In general, skin and soft tissue infections are the most common and bacteremia or septic metastasis are frequent. In contrast to previous Spanish studies, more cases are observed in patients born in Spain and the infections are more severe.

 
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Rev Esp Quimioter 2011:24(1):4-12

Proton pump inhibitors and infection risk 

E. PALENCIA-HERREJÓN, B. SÁNCHEZ, I. ESCOBAR, M. L. GÓMEZ-LUS   

 

Gastric antisecretory drugs, especially proton pump inhibitors, are among the most used drugs both in ambulatory and hospital settings, and prescription does not always follows approved indications. Experimental data suggest that gastric acid inhibition and the effects of proton pump inhibitors on the immune system can promote the development of infections. In recent years a number of observational studies have found an independent association between the use of proton pump inhibitors and an increased risk of gastrointestinal infections, including those caused by Clostridium difficile, and community and nosocomial pneumonia. This review discusses the current evidence, raises the potential pathogenic mechanisms involved and makes recommendations for current clinical practice and future research.    

 
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Rev Esp Quimioter 2011:24(3):127-130

In vitro activity of retapamulin against linezolid and methicillin–resistant Staphylococcus aureus isolates       

F. J. CANDEL, G. MORALES, J. J. PICAZO           

 

 

Objectives: To determine the in vitro activity of retapamulin and other topical antibiotics (mupirocin, bacitracin, and fusidic acid) usually employed for nasal decolonization, against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and linezolid and methicillin–resistant S. aureus.
Methods: The minimum inhibitory concentrations (MICs) were determined on Mueller-Hinton agar according to the guidelines of the Clinical and Laboratory Standards Institute and of the European Committee for Antimicrobial Susceptibility Testing. Presence of the cfr gene in linezolid and methicillin–resistant S. aureus isolates was detected using polymerase chain reaction.
Results: Retapamulin inhibited all the isolates of MSSA and MRSA at 0.125 mg/L, but the 18 linezolid-resistant-MRSA strains proved resistant, with MICs over 32 mg/L. Most MSSA isolates (9/10) were susceptible to mupirocin with MICs under 0.19 mg/L, although this value decreased to half against MRSA, and almost all linezolid-resistant MRSA (17/18) strains were resistant to mupirocin with an MIC range of between 8 mg/L and 28 mg/L. The MIC of fusidic acid increased substantially against linezolid-resistant MRSA, whereas that of bacitracin showed no differences.
Conclusions: Retapamulin demonstrated excellent in vitro activity against MSSA and MRSA strains, but not against MRSA isolates harbouring the cfr gene. The results of this in vitro study support cut-off values for retapamulin of ≤ 0.5, 1, and ≥ 2 mg/L for susceptible, intermediate, and resistant strains, respectively.

 
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Rev Esp Quimioter 2011:24(4):263-270

Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient                

J. BARBERÁN, J. MENSA, J. C. VALLEJO, I. JARQUE, J. C. GARCÍA, J. R. CABRERA, P. BALTASAR, J. BESALDUCH, J. M. CALVO, F.  J.  CAPOTE, E. CARRERAS, M. L. DÍAZ, F. ESCALANTE, P. FERNÁNDEZ, S. GARZÓN, C. GRANDE, D. HERNÁNDEZ, A. LÓPEZ, J. LÓPEZ, E. MARTÍN, M. OLAVE, J. PÉREZ, G. RAMÍREZ, R. ROJAS, A. ROMÁN, M. ROVIRA, D. RUBIO, P. SÁNCHEZ , A. SÁNCHEZ, J. DE LA SERNA, C. SOLANO, D. VALCÁRCEL, J. M. AGUADO, J. R. AZANZA, R. CANTÓN , R. CISTERNA, J. DÍAZ, J. FORTÚN, J. GARCÍA, J. GÓMEZ, E. GÓMEZ, J.  M. MONTEJO, F. J. PEMÁN, I. RUIZ, M. SALAVERT, M. A. SANZ, J. DE LA TORRE, L. VÁZQUEZ                        

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results. 

 
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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.  

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Rev Esp Quimioter 2010:23(2):103-108

A combination of tigecycline, colistin, and meropenem against multidrug-resistant Acinetobacter baumannii bacteremia in a renal transplant recipient: pharmacodynamic and microbiological aspects  

F.J. CANDEL, N. CALVO, J. HEAD, A. SÁNCHEZ, M. MATESANZ, E. CULEBRAS, A. BARRIENTOS, J. PICAZO 

 

Acinetobacter baumannii are emerging as the causal agents of healthcare-associated infections. We describe a renal transplant recipient who developed bacteremia caused by multiresistant A. baumannii, which received a combination of tigecycline, colistin, and meropenem in continuous infusion. The clinical outcome was favorable. In this article we made a molecular study of this multiresistant strain. Our analysis reveals the presence of a bla-OXA-72 gene, a class D of oxacillinase belonging to bla-OXA-40-like group, which constitutes the most disseminated familiy of carbapenemases in Spain. Thus, we found different susceptibility patterns of A. baumannii when we used different Mueller-Hinton agars with different manganese concentrations. Lastly, we explain the combination of these three antibiotics administered to increase microbiologic and pharmacodynamic yield.

 
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Rev Esp Quimioter 2011:24(1):13-24

Role of daptomycin in the empirical and directed therapy of infections caused by Gram-positive bacteria in the critically ill patient

J. GARNACHO-MONTERO, R. AMAYA-VILLAR, M. L. GÓMEZ-GRANDE, V. JEREZ, L. LORENTE-RAMOS, A. LOZA, A. MARTÍNEZ, J. C. POZO, R. SIERRA, J. POMARES, M. V. DE LA TORRE, C. ORTIZ   

 

Infections caused by Gram-positive bacteria are a serious problem and is associated with high mortality. Among them, we should highlight those caused by methicillin-resistant Staphylococcus aureus (MRSA). Primary bacteremia, catheter-related bloodstream infections and constitute the main presentations. Vancomycin has traditionally been the treatment of choice for these infections, but its activity is not satisfactory especially in cases of MRSA with minimum inhibitory concentration (MIC) > 1 mg/L. Daptomycin is a lipopeptide antibiotic active against Gram-positive bacteria including MRSA and glycopeptide-resistant Enterococcus spp.It is worth mentioning that daptomycin is rapidly bactericidal against methicillin-sensitive S. aureus, more potent than vancomycin and at least as active as isoxazole penicillins. This article discusses the role of this antibiotic in the empirical treatment of infections and directed by Gram-positive bacteria affecting critically ill patients.    

 
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Rev Esp Quimioter 2013:26(1):64-69

Treatment of invasive fungal infections in high risk hematological patients. The outcome with liposomal amphotericin B is not negatively affected by prior administration of mold-active azoles
                           

J. DE LA SERNA, I. JARQUE, J.LÓPEZ-JIMÉNEZ,  J.M. FERNÁNDEZ-NAVARRO, V. GÓMEZ, M. JURADO, A. PASCUAL, J. SERRANO, M. ROMERO, C. VALLEJO                         

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.

Rev Esp Quimioter 2013:26(1):64-69 [pdf]

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