Rev Esp Quimioter 2014:27(1):51-55

In vitro emergence of ertapenem resistance in Escherichia coli producing extended-spectrum β-lactamase                                
 

HUGO E. VILLAR, MÓNICA B JUGO, MATÍAS VISSER, MARIANA HIDALGO, GABRIEL HIDALGO, GUSTAVO CESAR MACCALLINI               

Introduction. The occurrence of community-associated infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. These organisms are frequently resistant to many of the antimicrobial agents but remain susceptible to carbapenems. We investigated the in vitro emergence of carbapenem resistance in a collection of clinical isolates of ESBL -producing E. coli.
Material and methods. First and second-step resistant mutants were obtained from E. coli with ESBL. Aliquots of 50μl containing > 109 CFU were applied to Mueller-Hinton plates containing meropenem, imipenem or ertapenem. MICs for native strains and mutants were determined using the epsilometric test (E-test).
Results. Resistant mutants were not selected with imipenem or meropenem. E. coli growth was observed on ertapenem (0.5 mg/L)-containing plates in 13 of 57 clinical isolates (22.8 %).The ertapenem MIC for these first-step mutants were ≥ 1 mg/L, remaining susceptible to imipenem and meropenem. The first-step mutants were used as native strains. Six second-step resistant mutants were selected with ertapenem. All were fully resistant (CMI ≥ 8 mg/L) to ertapenem, three were resistant to meropenem and one to imipenem. Four second-step resistant mutants were selected with meropenem. All were resistant to ertapenem, meropenem, and two of them were resistant to imipenem.
Conclusions. Stable resistant mutants were easy to select with ertapenem among ESBL-producing E. coli. Two steps were necessary to select resistant mutants to meropenem or imipenem.The use of ertapenem in high-inoculum infections or in undrained focus of infection should be monitored to reduce the risk on selection of resistance.

Rev Esp Quimioter 2014:27(1):51-55 [pdf]

Rev Esp Quimioter 2014:27(3):196-212

EPICO 2.0 PROJECT. Development of educational therapeutic recommendations using the DELPHI technique on invasive candidiasis in critically ill adult patients in special situations                                 
 


RAFAEL ZARAGOZA, RICARD FERRER, EMILIO MASEDA, PEDRO LLINARES, ALEJANDRO RODRIGUEZ ON BEHALF OF THE EPICO PROJECT GROUP       
        

Introduction. Although there has been an improved management of Invasive Candidiasis in the last decade, still controversial issues remain, especially in different therapeutic critical care scenarios.
Objectives. We sought to identify the core clinical knowledge and to achieve high agreement recommendations required to care for critically ill adult patients with Invasive Candidiasis for antifungal treatment in special situations and different scenarios.
Methods. Second Prospective Spanish survey reaching consensus by the Delphi technique, conducted anonymously by electronic e-mail in the first phase to 23 national multidisciplinary experts in invasive fungal infections from five national scientific societies including Intensivists, Anesthesiologists, Microbiologists, Pharmacologists and Infectious disease specialists, answering 30 questions prepared by a coordination group after a strict review of literature in the last five years. The educational objectives spanned four categories, including peritoneal candidiasis, immunocompromised patients, special situations and organ failures. The agreement among panellists in each item should be higher than 75% to be selected. In a second phase, after extracting recommendations from the selected items, a meeting was heldwith more than 60 specialists in a second round invited to validate the preselectedrecommendations.
Measurements and Main Results. In the first phase, 15 recommendations were preselected (peritoneal candidiasis (3), immunocompromised patients (6), special situations (3) and organ failures (3)). After the second round the following 13 were validated: Peritoneal candidiasis (3): Source control and early adequate antifungal treatment is mandatory; empirical antifungal treatment is recommended in secondary nosocomial peritonitis with Candida spp colonization risk factors and in tertiary peritonitis. Immunocompromised patients (5): Consider hepatotoxicity and interactions before starting antifungal treatment with azoles in transplanted patients; treat candidemia in neutropenic adult patients with antifungal drugs at least 14 days after the first negative blood culture and until normalization of neutrophil count is achieved. Caspofungin, if needed, is the echinocandin with most scientific evidence to treat candidemia in neutropenic adult patients; Caspofungin is also the first choice drug to treat febrile candidemia; in neutropenic patients with candidemia remove catheter. Special situations (2): In moderate hepatocelular failure, patients with invasive candidiasis use echinocandins (preferably low doses of anidulafungin and caspofungin) and try to avoid azoles; in case of possible interactions review all of the drugs involved and preferably use Anidulafungin. Organ failures (3): Echinocandins are the safest antifungal drugs; reconsider the use of azoles in patients under renal replacement therapy; all of the echinocandins are accepted for the treatment of patients under continuous renal replacement therapy and do not require dosage adjustment.
Conclusions. Treatment of Invasive Candidiasis in ICU patients requires a broad range of knowledge and skills as summarized in our recommendations. These recommendations may help to optimize the therapeutic management of these patients in special situations and different scenarios and improve
their outcome based on the DELPHI methodology.

Rev Esp Quimioter 2014:27(3):196-212 [pdf]

Rev Esp Quimioter 2014:27(1):56-62

C. albicans, C. parapsilosis and C. tropicalis invasive infections in the PICU: clinical features, prognosis and mortality                                
 

IOLANDA JORDAN, LLUÏSA HERNANDEZ, MÓNICA BALAGUER, JOSÉ-DOMINGO LÓPEZ-CASTILLA, LIDIA CASANUEVA, CRISTINA SHUFFELMAN, MARÍA-ANGELES GARCÍA-TERESA, JUAN-CARLOS DE CARLOS, PALOMA ANGUITA, LORENZO AGUILAR, ON BEHALF OF THE ERICAP STUDY GROUP               

Candida albicans remains the most common agent associated with invasive Candida infection (ICI), but with increasing
number of non-albicans species. An epidemiological, observational study exploring host criteria, clinical characteristics and mortality of ICI was performed in 24 pediatric intensive care units (PICU) in Spain. Patients were analyzed in global and distributed by infecting species (for groups with ≥15 patients). A total of 125 ICI were included: 47 by C. albicans, 37 by C. parapsilosis, 19 by C. tropicalis, 4 C. glabrata, and 18 others. Up to 66% of ICI by C. albicans and 75.7% by C. parapsilosis occurred in children ≤24 months, while the percentage of children >60 months was higher in ICI by C. tropicalis. Bloodstream infection was most common among C. tropicalis (78.9%) or C. parapsilosis (83.8%) ICI, but urinary infections were almost as common as bloodstream infections among C. albicans ICI (31.9% and 38.3%, respectively). Fever refractory to antimicrobials was the most frequent host criterion (46.4% patients), but with equal frequency than prolonged neutropenia in C. tropicalis ICI. Thrombopenia was more frequent (p<0.05) in C. parapsilosis (60.7%) or C. tropicalis (66.7%) ICI than in C. albicans ICI (26.5%). Uremia was more frequent (p<0.05) in C. albicans (78.3%) or C. tropicalis (73.3%) than in C. parapsilosis ICI (40.7%). Multiple organ failure and heart insufficiency was higher in C. tropicalis ICI. Short duration (≤7 days) of PICU stay was more frequent in C. albicans ICI. Mortality rates were: 8.5% (C. albicans ICI), 13.5% (C. parapsilosis ICI) and 23.3% (C. tropicalis ICI). ICI by different Candida species showed different clinical profiles and mortality, making essential identification at species level.

Rev Esp Quimioter 2014:27(1):56-62 [pdf]

Rev Esp Quimioter 2014:27(4):239-243

Characterization of gene expression associated with both the AcrAB/TolC system and the membrane permeability, in Salmonella spp isolates with and without gyrA mutation                                 
 


ANTONIO GALIANA, LAURA SÁNCHEZ-GUILLÉN, JUAN CARLOS RODRÍGUEZ, ROSA CREMADES, MIGUEL SANTIBAÑEZ, RAFAELA FERRARI, MONTSERRAT RUIZ-GARCÍA, PILAR LÓPEZ, GLORIA ROYO       
        

Introduction. The marA, soxS, ramA, acrB and ompF genes have been studied in order to characterize mechanisms of AcrAB-TolC active efflux pumps and membrane permeabilityalterations that reduce fluoroquinolones susceptibility in Salmonella spp.
Methods. Mutations in marA, soxS, ramA, acrB and ompF genes were detected, as well as their expression levels in presence and absence of ciprofloxacin, calculating the level of change between them by qPCR. Data were analysed by using SPSS 19.0.
Results. No mutations in these genes were found, but both AcrAB-TolC regulatory genes and structural acrB gene expression were affected by ciprofloxacin in both mutant strains and wild type bacterial strains (WT). The activation of the marA gene in presence of drug was higher in WT strains (level of change 0.823) than in mutants strains (level of change 0.158; p=0.049). In gyrA mutants, a reduction in ompF gene expression in presence of ciprofloxacin was found (level of change -0.949 p=0.017).
Conclusion. The reduction of fluoroquinolones susceptibility in Salmonella spp is a complex process, in which several different bacterial mechanisms are involved. This study has found a high difference in the degree of participation among studied mechanisms, between bacterial strains with and without gyrA mutation. Whereas WT strains activated efflux pumps especially through marA gene, mutants supressed ompF gene expression related to porins.

Rev Esp Quimioter 2014:27(4):239-243 [pdf]

Rev Esp Quimioter 2014:27(1):69-86

Guidelines for the management of community-acquired pneumonia in the elderly patient                                 
 

JUAN GONZÁLEZ-CASTILLO, FRANCISCO JAVIER MARTÍN-SÁNCHEZ, PEDRO LLINARES, ROSARIO MENÉNDEZ, ABEL MUJAL, ENRIQUE NAVAS, JOSÉ BARBERÁN               

The incidence of community-acquired pneumonia (CAP) increases with age and is associated with an elevated morbimortality due to the physiological changes associated with aging and a greater presence of chronic disease. Taking into account the importance of this disease from an epidemiological and prognostic point of view, and the enormous heterogeneity described in the clinical management of the elderly, we believe a specific consensus document regarding this patient profile is necessary. The purpose of the present work was to perform a review of the evidence related to the risk factors for the etiology, the clinical presentation, the management and the treatment of CAP in elderly patients with the aim of elaborating a series of specific recommendations based on critical analysis of the literature. This document is the fruit of the collaboration of different specialists representing the Spanish Society of Emergency Medicine and Emergency Care (SEMES), the Spanish Society of Geriatrics (SEG), the Spanish Society of Chemotherapy (SEQ), the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) and the Spanish Society of Home Hospitalization (SEHAD).

Rev Esp Quimioter 2014:27(1):69-86 [pdf]

Rev Esp Quimioter 2014:27(4):244-251

Prospective follow-up of results of tuberculosis treatment                                 
 


MARTA MORENO-GÓMEZ, MONTSERRAT ALONSO-SARDÓN, HELENA IGLESIAS-DE-SENA, LUCIANA LUCENA ARANHA DE MACÈDO       
        

Objective. The aim of the study was to analyze tuberculosis treatment outcomes in a health area of the National Health System.
Material and Methods. Analytical cohort study of tuberculosis’ cases treated in the hospital care of the health area of Salamanca (Spain) 6 months. The clinical record constituted the basic source of data, whose information was complemented by a clinical interview to the patient. The microbiological records were additionally used for classifying the therapeutic outcomes in satisfactory outcome (SO), potentially unsatisfactory outcome (PUO) and death. A total of 146 patients met the inclusion criteria; 108 patients were interviewed. Their average age was 49 years. Out of them, 29.6% (32/108) showed some social risk factor (SRF).
Results. The SO level was 55.6% (IC 95%: 55.6±9); the variables associated with the SO were young elderly patients, living in family and patterns of 6 months. The PUO proportion stood at 40.7% (IC 95%: 40.7±9); the variables which increased the PUO probability were adulthood, residing in other provinces, living alone, comorbidity, human immunodeficiency virus (HIV), alcoholism and social maladjustment. The variables included in the final model for PUO in logistic regression were adult, comorbidity and SFR, while the institutional conditions associated the mortality.
Conclusions. The SO rates can be improved. The PUO level is conditioned by high loss rates, 31.5% (95% CI: 31.5 ± 9), so measures should be established for reduction and improve the effectiveness of the overall treatment.

Rev Esp Quimioter 2014:27(4):244-251 [pdf]

Rev Esp Quimioter 2014:27(2):87-92

Detection of antibacterial resistance by MALDI-TOF mass spectrometry                                 
 

YULIYA ZBOROMYRSKA, MARIO FERRER-NAVARRO, FRANCESC MARCO, JORDI VILA               

In the last decade we have witnessed a remarkable increase in the number of strains isolated in hospitals that are producing extended spectrum β-lactamases (ESBL) or, more recently, carbapenemases. This makes clear the need for a system for rapid detection of these resistance mechanisms that allow the selection of the most suitable antibiotic treatment in order to improve patient care. Recent data support the possibility of using mass spectrometry (MS), specifically MALDI-TOF (Matrix-Assisted Laser Desorption / Ionization, Time-of-Flight ) systems to identify specific resistance mechanisms and their use offers several advantages. First, the economic cost of each determination is clearly inferior to the classical molecular techniques for detection of resistance genes. Second, detection of resistance by MALDI-TOF reduces the time for obtaining results compared to the routine methods currently employed. Finally, the possibility that this method allow us to detect enzymes not previously characterized, that there is no information about the genes that encode them. Therefore, we believe that this may be a good tool to implement in clinical microbiology laboratories. This review aims to present the latest developments in this field.

Rev Esp Quimioter 2014:27(2):87-92 [pdf]

Rev Esp Quimioter 2014:27(4):252-260

Empirical antimicrobial therapy in ICU admitted patients. Influence of microbiological confirmation on the length of treatment                                 
 


XAVIER NUVIALS, ELENA ARNAU, JOAQUIM SERRA, ROSA ALCARAZ, JESÚS CABALLERO, CÉSAR LABORDA, MARCOS PÉREZ, M. NIEVES LARROSA, MERCEDES PALOMAR       
        

Introduction. Most patients admitted to the Intensive Care Units (ICU) receive antimicrobial treatment. A proper therapeutic strategy may be useful in decreasing inappropriate empirical antibiotic treatments. When the infection is not microbiologically confirmed, the antimicrobial streamlining may be difficult. Nevertheless, there is scant information about the influence of the microbiological confirmation of the infections on empirical antimicrobial treatment duration.
Method. Post-hoc analysis of prospective data (ENVIN-UCI register) and observational study of patients admitted (> 24 hours) in a medico-surgical ICU, through the three-months annual surveillance interval for a period of ten years, receiving antimicrobial treatment for treating an infection. Demographic, infection and microbiological data were collected as well as empirical antimicrobial treatment and causes of adaptation. The main goal was to establish the influence of microbiological confirmation on empirical antimicrobial treatment duration.
Results. During the study period 1,526 patients were included, 1,260 infections were diagnosed and an empirical antibiotic treatment was started in 1,754 cases. Infections were microbiologically confirmed in 1,073 (62.2%) of the empirical antibiotic treatment. In 593 (55.3%) cases, the antimicrobial treatment was considered appropriate. The main cause of treatment adaptation in the microbiologically confirmed infections was streamlining (39%). The microbiological confirmation of the infection was not associated with significantly shorter empirical antibiotic treatments (6.6 ± 5.2 VS. 6.8 ± 4.5 days).
Conclusion. The microbiological confirmation of infections in patients admitted to UCI was associated with a higher reduction of antimicrobial spectrum, although had no effect on the length of empirical antimicrobial therapy.

Rev Esp Quimioter 2014:27(4):252-260 [pdf]

Rev Esp Quimioter 2014:27(2):93-97

Reasons for antiretroviral treatment change in HIV+ patients in Spain in 2010-2011. SWITCH AUDIT Study                                 
 

ENRIC PEDROL, POMPEYO VICIANA, ALBERTO ARRANZ, JUAN PASQUAU, ELISABETH DEIG, MARIONA TASIAS Y EL GRUPO DE ESTUDIO SWITCH AUDIT               

Survey in 349 HIV infected subjects in 19 Spanish Hospitals in 2010-2011, to assess the reasons for antiretroviral treatment change. Simplification was the most frequent reason for change (37%), followed by toxicity (30%) and treatment failure (21%). There were statistically significant differences according to treatment line and transmission category. In conclusion, in many patients treatment is changed in order to obtain the benefits of a regimen easier to follow.

Rev Esp Quimioter 2014:27(2):93-97 [pdf]

Rev Esp Quimioter 2014:27(4):261-268

Trend in the susceptibility of the most frequent bacterial pathogens isolated at Hospital General La Mancha Centro over 2010-2012 period                                 
 


MARÍA ÁNGELES ASENCIO, MARÍA HUERTAS, RAFAEL CARRANZA, MARÍA FRANCO, JESÚS CASTELLANOS, JOSÉ RAMÓN BARBERÁ, MARÍA DEL CARMEN CONDE, JOSÉ MARÍA TENÍAS      
        

Introduction. Our objective was to determine the trend of the antimicrobial susceptibility of the most common bacterial
pathogens isolated in La Mancha Centro Hospital (MCH) between 2010-2012.
Material and methods. Isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa from patients admitted to MCH were studied. These data and their antibiotic susceptibility were obtained from the database OBSERVA (BioMérieux).
Results. The percentages of susceptibility for S. aureus were: 50% methicillin-resistant-S. aureus (MRSA) (higher co-resistance to erythromycin and levofloxacin), 46% erythromycin, 73% clindamycin, 45% levofloxacin, 99% rifampin and 100% cotrimoxazole, glycopeptides, linezolid and daptomycin. Increased resistance in ICU was observed (63% MRSA), with 50% of S. aureus (susceptible and methicillin-resistant strains) with vancomycin MIC values ≥ 0.5 mg/L. E. coli susceptibility: 62% amoxicillin-clavulanate, 55% ciprofloxacin, 60% cotrimoxazole, 84% gentamicin and 95% fosfomycin. K. pneumoniae susceptibility: 74% amoxicillin-clavulanate, 71% ciprofloxacin, 78% cotrimoxazole, 94% gentamicin and 87% fosfomycin. The percentage of BLEE strains was 17% and 21% for E. coli and K. pneumoniae, respectively, without detection of resistance to carbapenems. P. aeruginosa susceptibility: 80% ceftazidime and carbapenems, 63% ciprofloxacin and higher than 90% aminoglycosides. A decreasing trend of susceptibility to ceftazidime and carbapenems was observed in ICU and increasing trend to ciprofloxacin.
Conclusions. Resistance percentages were higher in ICU than in the rest of the hospital, highlighting 63% of MRSA strains. Our percentage of BLEE and MRSA strains were higher than the Spanish media. Rifampicin and cotrimoxazole maintain good susceptibility to S. aureus, fosfomycin and aminoglycosides to Enterobacteriaceae and carbapenems to P. aeruginosa.

Rev Esp Quimioter 2014:27(4):261-268 [pdf]