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 2013:26(2):103-107

Reasons for the introduction of darunavir in the antirretroviral treatment in HIV-infected patients                                
 

ENRIC PEDROL, JUAN CARLOS LÓPEZ-BERNALDO DE QUIRÓS, SHEILA RUIZ, HENAR HEVIA, FRANCISCO LEDESMA             

Introduction. In 2009 a deep change in ARV treatment took place in Spain with the introduction of new ARV drugs.The principal objective of the study was to determine the clinical situation of the patients in which DRV/r was introduced in the ARV therapy.
Methods. Observational, cross sectional and multicentre study in which 91 reference hospitals participated. Patient’s enrolment was carried out between 2008 and 2009. Data were collected retrospectively considering standard clinical practice.
Results. 719 medical records were reviewed. Patients had a different clinical situation compared to nowadays with predominance of multiresistant virus which leaded to virologic failure. The principal reason for introducing DRV/r in the ARV regimen was the virologic failure (54.2%).
Conclusions. Considering this situation, DRV/r became a therapeutic option which represented a change in the ARV paradigm in that period.

Rev Esp Quimioter 2013:26(2):103-107 [pdf]

Rev Esp Quimioter 2013:26(4):298-311

Prevention and control of nosocomial and health-care facilities associated infections caused by species of Candida and other yeasts

JAVIER PEMÁN, RAFAEL ZARAGOZA, MIGUEL SALAVERT             

Knowledge of the epidemiology of invasive fungal diseases caused by yeasts (Candida spp., especially) in health care settings allows the establishment of the levels necessary for its prevention. A first step is to identify groups of patients at high risk of nosocomial invasive fungal infections, establish accurate risk factors, observing the periods of greatest risk, and analyze the epidemiological profile in genera and species as well as the patterns of antifungal resistance. Secondly, mechanisms to avoid persistent exposure to potential fungal pathogens must be programed, protecting areas and recommending measures such as the control of the quality of the air and water, inside and outside the hospital, and other products or substances able to cause outbreaks. Finally, apart from the correct implementation of these measures, in selected patients at very high risk, the use of antifungal prophylaxis should be considered following the guidelines published.

Rev Esp Quimioter 2013:26(4):298-311 [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 2009:22(4):221-223

Cellulitis after a cat bite

J. PÉREZ, F. J. CANDEL, E. BAOS, F. GONZÁLEZ, J. J. PICAZO

Animal bite wounds are common. Domestic companion animals inflict the majority of these wounds. The most important percentage of contagions are due to catbites, and often by Pasteurella species. We present two cases of Pasteurella multocida infection after a cat bite. Thus, in this article we review the most relevant clinical features related with this aetiological agent and some aspects about antimicrobial susceptibility.

Rev Esp Quimioter 2009:22(4):221-223 [pdf]

Rev Esp Quimioter 2009:22(4):214-220

Influenza surveillance by molecular methods

A. TENORIO, J. M. EIROS, E. RODRÍGUEZ, J. F. BERMEJO, M. DOMÍNGUEZ, T .VEGA, J. CASTRODEZA, R. ORTIZ

 

Introduction: Our objective was to evaluate the application of molecular techniques in the surveillance of influenza, and to describe clinical and epidemiological characteristics of cases diagnosed in 2007-2008 and2008-2009 seasons.

Methods: We analyzed 183 pharyngeal swabs from the same number of patients referred to the virology laboratory of the Sentinel Physician Network of Castilla y Leon, the study of influenza viruses by shell-vial technique and RT-PCR capable of detecting multiple Simultaneously, influenza virus A, B, C, respiratory syncytial virus A, B and adenovirus.

Results: Using cell culture were isolated 17 influenza A viruses and 19 influenza B viruses (19.7% of total). By multiple RT-PCR, was detected 49 influenza A virus, 29 influenza B virus, an influenza virus C, 3 syncytial virus type A and other B and 6 adenoviruses (44.3% of total). All influenza viruses isolated in cell culture was detected by RT-PCR. RT-PCR by 5 co-infections were detected, which represented a 6.25% of co-infections on the whole of positive samples. The average age of patients was 29 years (SD = 21.07). The proportion of women and men accounted for 43.7% and 56.3% respectively. The number of cases diagnosed in relation to age follows a pattern of negative linear correlation.

Conclusions: RT-PCR is revealed as an useful tool for epidemiological surveillance of influenza, allowing also to detect viral subtypes along with other viruses involved in respiratory infections.

Rev Esp Quimioter 2009:22(4):214-220 [pdf]  

Rev Esp Quimioter 2009:22(4):210-213

Assessment of the antibiotic allergy questionnaire in the medical history

M. DELGADO, R. ICART, L. RIBÓ, A. SÁNCHEZ, X MARTÍNEZ-COSTA, M. MAURI, J. A CAPDEVILA

 

Objectives: Antibiotic allergy questionnaire is a useful tool for prescribing antibiotics. The objective of this study is to assess the prevalence and clinical reliability of antibiotic allergy in medical records.

Patients and method: Observational analysis of clinical records. Assessment of antibiotic allergy by direct interview conducted by the investigator.

Results: 610 medical records were evaluated. Antibiotic allergy was checked in 98%, mainly in medical wards.  In 12 % of patients, antibiotic allergy was suspected, but after investigator interview only 5% of patients fulfilled clinical criteria for allergy. 44% of falses allergies were recorded. The most frequent cause of con-fusion was faint and gastric intolerance.

Conclussion: The questionnaire about antibiotic allergy is present in almost all medical records. However its reliability is low, less than 50%. Prevalence of veritable antibiotic allergy is 5% in this study. Antibiotic allergy questionnaire in medical records is a practical tool. However periodical training about antibiotic allergy definition is necessary for nurses and medical staff.

 
Rev Esp Quimioter 2009:22(4):210-213 [
pdf]

Rev Esp Quimioter 2009:22(4):207-209

Evaluation of three Immunochromatographic Assays for Detection of Legionella pneumophila serogroup 1 Antigen in Urine Samples

M. J. MUÑOZ, M.C. MARTÍNEZ, G. YAGÜE, M. SEGOVIA

 

The Uni-Gold, the SAS and the Binax NOW immunochromatographic test (ICT) urinary antigen assays for the qualitative detection of Legionella pneumophila serogroup 1 were compared using 39 unfrozen and nonconcentrated urine samples from patients with Legionnaires´disease (LD). The Uni-Gold anti-gen test detected the urinary antigen in 41% (16/39), the SAS antigen test in 61.5% (24/39), and the Binax NOW antigen test in 74.3% (29/39). The Binax NOW ICT assay showed the best results when detecting L. pneumophila urinary antigen.

Rev Esp Quimioter 2009:22(4):207-209 [pdf]