Rev Esp Quimioter 2014:27(2):106-109

First clinical isolate in Europe of clindamycin-resistant group B Streptococcus mediated by the lnu(B) gene                                 
 

 DAVID M ARANA, BEATRIZ ROJO-BEZARES, CARMEN TORRES, JUAN IGNACIO ALÓS               

We characterize the mechanisms implicated in an unusual phenotype of resistance to macrolides-lincosamides (no halos of inhibition around clindamycin and lincomycin discs, and a 15 mm halo around erythromycin disc) in a Streptococcus agalactiae isolate recovered in Spain. The presence of macrolide or lincosamide resistance genes [erm(A),erm(B), erm(C), erm(T), mef(A), mrs(A), lnu(A), lnu(B), lsa(B), lsa(C) and vga(C)] was investigated by PCR and sequencing. The strain showed a resistant phenotype to erythromycin and clindamycin (MIC = 2 mg/L and MIC = 8 mg/L, respectively) and the presence of lnu(B) and mef(A) genes was demonstrated. Clinical microbiology laboratories should be aware of this unusual phenotype due to the association of two mechanisms mediated by lnu(B) and mef(A) genes. This constitute, to our knowledge, the first report of lnu(B) in S. agalactiae in human isolates in Europe.

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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.

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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.

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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.

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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.

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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.

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Rev Esp Quimioter 2014:27(3):190-195

Prevalence and risk factors for meticillin-resistant Staphylococcus aureus in an acute care hospital and long-term care facilities located in the same geographic area                                 
 


M. PILAR BARRUFET, ESTER VENDRELL, LLUIS FORCE, GORETTI SAUCA, SANDRA RODRIGUEZ, ENCARNA MARTINEZ, ELISABET PALOMERA, MATEU SERRA-PRAT,  JOSEP ANTON CAPDEVILA, JORDI CORNUDELLA, ANABEL LLOPIS, M. ASUNCIÓN ROBLEDO, CRISÓSTOMO VAZQUEZ               

To determine the prevalence and risk factors (RF) for methicillin-resistant Staphylococcus aureus (MRSA) during stay in 1 acute care hospital (ACH) and 4 long-term care facilities (LTCF). After obtaining the informed consent, nasal and skin ulcer swabs were taken and a survey was conducted to determine RF for MRSA. Six hundred and ninety nine patients were included, 413 LTCF and 286 ACH patients and MRSA prevalence were 22.5% and 7.3% respectively. MRSA was located in the nares, skin ulcers, and in both in 61.4%, 21.1%, and 17.5%. Among MRSA carriers, 81% of the ACH and 66.7% of the LTCF patients were only colonized. The multivariate analysis for the ACH revealed the following factors to be associated with MRSA: referral from an LTCF (OR 4.84), pressure ulcers (OR 4.32), a Barthel score < 60 (OR 2.60), and being male (OR 5.21). For the LTCF: urinary catheterisation (OR 3.53), pressure ulcers (OR 2.44), other skin lesions (OR 2.64), antibiotic treatment in ≤ 6 months, (OR 2.23), previous MRSA colonization (OR 2.15), and a Barthel score <20 (OR 1.28). Molecular typing identified 2 predominant clones Q, P, present in all centres. No relationship was found between clones and antibiotic susceptibility.
In conclusion: MRSA prevalence is high in all centres but is 3 times greater in LTCF. The risk factors most strongly associated with MRSA were pressure ulcers and a stay in an LTCF. We propose preventive isolation in these cases.

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Rev Esp Quimioter 2014:27(3):180-189

State of infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in Extremadura: susceptibility, clonality and role of community-associated MRSA                                 
 


VICENTE AGUADERO, CARMEN GONZÁLEZ-VELASCO, ANA VINDEL, MIGUEL GONZÁLEZ-VELASCO, JUAN JOSÉ MORENO               

The correct surveillance and control of infection caused by methicillin-resistant Staphylococcus aureus (MRSA) needs of update knowledge of its specific properties in each place. Our study aims to describe the current characteristics of infection due to MRSA in Extremadura. During 2010, 309 MRSA were collected from clinical samples in our region. A susceptibility test that included 17 antibiotics tested by AST -588 card Vitek 2 ® and E -test method was performed on all isolates. A sample of 100 strains, selected by stratified random sampling, were genotyped by pulsed field electrophoresis (PFGE). The prevalence of MRSA in Extremadura was 20.2%. Don Benito-Villanueva area showed the most prevalence and a higher incidence. Merida reported the most favourable situation, with a relatively low ratios of prevalence and incidence. The community acquired reached 44 % in the region, showing predominantly in less populated areas (Navalmoral and Coria). The most common multiresistant pattern was tobramycin-levofloxacin-erythromycin (44%), followed tobramycin-erythromycin-clindamycin (20%). No linezolid, daptomycin and tigecycline resistant strains were observed, but 42 % of the MRSA strains showed decreased susceptibility vancomycin (DSV). PFGE analysis reported 27 genotypes, with 3 major genotypes: E8a (25%), E7b (17%) and E7a (12%). The post-hoc statistical analysis did not reveal significant differences in the distribution of genotypes between different areas. However it revealed some trends that should be considered.

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Rev Esp Quimioter 2014:27(3):170-179

Reduction in diabetic amputations over 15 years in a defined Spain population. Benefits of a critical pathway approach and multidisciplinary team work                                 
 

DIEGO DE ALCALÁ MARTÍNEZ-GÓMEZ, M. ANGELES MORENO-CARRILLO, ALVARO CAMPILLO-SOTO, ANDRÉS CARRILLO-GARCÍA, JOSÉ LUÍS AGUAYO-ALBASINI               

Objective. To assess changes in diabetic lower-extremity amputations (LEA) rates in a defined population over a 15-year period, following a multidisciplinary approach including a critical pathway in an inpatient setting with standardized preoperative and postoperative care, as well as in an outpatient setting through the establishment of a diabetic foot clinic.
Methods. This is a study of the incidence and types of LEAs performed in patients with diabetic foot disease complicated admitted to Morales Meseguer Hospital (Murcia, Spain), a large district general hospital, before (1998-2000) and after (2001-2012) of the introduction of better organized diabetes foot care. Hospital and clinic characteristics to the success of the programme are described. All cases of LEA in diabetic patients (1998-2012) within the area were identified by ICD-9-Clinical modification (CM) diagnostic codes. A chi square test was used to compare the frequency and level of amputations.
Results. Over all inpatients with diabetes admitted with foot infections and gangrene, there was a significant decrease in the proportion of total major amputations (47%) and elective major amputations (66%) (p<0.001). The incidence of total major amputations rates per 100.000 of the general population fell with statistical significance (p=0.009). The biggest improvement in LEA incidence was seen in the reduction of major elective amputation with fell 60%, from 7.6 to 3.1 per 100,000 (p<0.001).
Conclusions. Significant reductions in total and major amputations rates occurred over the 15-year period following improvements in foot care services included multidisciplinary teamwork (critical pathway and diabetic foot clinic).

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Rev Esp Quimioter 2014:27(3):159-169

Pharmaceutical intervention in duration of antimicrobial treatment at hospital ambit                                 
 

MARÍA MORANTE, CARMEN MATOSES-CHIRIVELLA, FRANCISCO JOSÉ RODRÍGUEZ-LUCENA, JOSÉ MANUEL DEL MORAL, MONTSERRAT RUIZ-GARCÍA, ANDRÉS NAVARRO-RUIZ               

Objective. To estimate the acceptance of the pharmaceutical intervention in controlling duration of antimicrobial therapy
and to evaluate their impact on optimizing the treatment.
Methods. Prospective observational study for two years in a General University Hospital. For the patients record, we followed non critical adult patients with antibiotic treatment. When the duration of antimicrobial treatment not complied with established criteria for each antibiotic and pathology, there was a communication with the physician, at which is recommended to assess the need for continue treatment. The acceptance of pharmaceutical intervention was collected and afterwards we analyzed the impact of this work by antimicrobial consumption and incidence of Clostridium difficile.
Results. In 122 patients the pharmacist made a pharmaceutical intervention due to prolonged antibiotic treatment. The most prevalent antibiotics were β-lactams, specifically meropenem. The intravenous administration was more frequent. In 77 cases it was decided to recommend the suspension of treatment, we conducted an orally prospective intervention at 70.15 % and the rest of interventions were written. Acceptance was 65.95 % and 65.00%, respectively. During the study period, the DDD of the antimicrobials decreased by 8.89% and expenditure on antimicrobials one 40.12%. The incidence of C. difficile was stable.
Conclusions. In a hospital, a pharmaceutical counselling program on the duration of antimicrobial therapy is well accepted by the prescriber physician, but it must be improved. The route of information does not affect the degree of acceptance. These actions could involve a reduction of antimicrobial consumption.

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