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Rev Esp Quimioter 2019; 32(2): 156-164

Comparison of different strategies for short-term death prediction in the infected older patient

MARÍA CECILIA YAÑEZ, MANUEL SALIDO MOTA, MANUEL FUENTES FERRER, AGUSTÍN JULIÁN-JIMÉNEZ, PASCUAL PIÑERA, FERRÁN LLOPIS, JULIO GAMAZO DEL RIO, MIKEL MARTÍNEZ ORTIZ DE ZARATE, ÁNGEL ESTELLA, FRANCISCO JAVIER MARTÍN-SÁNCHEZ, JUAN GONZÁLEZ DEL CASTILLO, EN REPRESENTACIÓN DEL GRUPO DE INFECCIONES DE LA SOCIEDAD ESPAÑOLA DE MEDICINA DE URGENCIAS Y EMERGENCIAS (INFURG-SEMES)

Objective. The aim of this study was to determine the utility of a post hoc lactate added to SIRS and qSOFA score to predict 30-day mortality in older non-severely dependent patients attended for infection in the Emergency Department (ED).
Methods. We performed an analytical, observational, prospective cohort study including patients of 75 years of age or older, without severe functional dependence, attended for an infectious disease in 69 Spanish ED for 2-day three seasonal periods. Demographic, clinical and analytical data were collected. The primary outcome was 30-day mortality after the index event.
Results. We included 739 patients with a mean age of 84.9 (SD 6.0) years; 375 (50.7%) were women. Ninety-one (12.3%) died within 30 days. The AUC was 0.637 (IC 95% 0.587-0.688; p<0.001) for SIRS ≥ 2 and 0.698 (IC 95% 0.635-0.761; p<0,001) for qSOFA ≥ 2. Comparing receiver operating characteristic (ROC) there was a better accuracy of qSOFA vs SIRS (p=0.041). Both scales improve the prognosis accuracy with lactate inclusion. The AUC was 0.705 (IC95% 0.652-0.758; p<0.001) for SIRS plus lactate and 0.755 (IC95% 0.696-0.814; p<0.001) for qSOFA plus lactate, showing a trend to statistical significance for the second strategy (p=0.0727). Charlson index not added prognosis accuracy to SIRS (p=0.2269) or qSOFA (p=0.2573).
Conclusions. Lactate added to SIRS and qSOFA score improve the accuracy of SIRS and qSOFA to predict short-term mortality in older non-severely dependent patients attended for infection. There is not effect in adding Charlson index.

Rev Esp Quimioter 2019; 32(2): 156-164 [Texto completo PDF]

 

 

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Rev Esp Quimioter 2019; 32(2): 145-155

Monitoring the antimicrobial susceptibility of Gram-negative organisms involved in intraabdominal and urinary tract infections recovered during the SMART study (Spain, 2016 and 2017)

RAFAEL CANTÓN, ELENA LOZA, JAVIER AZNAR, FRANCISCO JAVIER CASTILLO, EMILIA CERCENADO, PABLO ARTURO FRAILE-RIBOT, FERNANDO GONZÁLEZ-ROMO, JOSÉ LUIS LÓPEZ-HONTANGAS, JESÚS RODRÍGUEZ-LOZANO, ANA ISABEL SUÁREZ-BARRENECHEA, FE TUBAU, JAZMÍN DÍAZ-REGAÑÓN, DIEGO LÓPEZ-MENDOZA AND THE SMART-SPAIN WORKING GROUP

Introduction. Continuous antimicrobial resistance surveillance is recommended by Public Health authorities. We up-dated data from the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain.
Material and methods. The antimicrobial susceptibility data and extended-spectrum beta-lactamase (ESBL) production in isolates recovered from intra-abdominal (IAI) (n=1,429) and urinary tract (UTI) (n=937) infections during the 2016- 2017 SMART study in 10 Spanish hospitals were analysed.
Results. Escherichia coli was the most frequently microorganism isolated (48.3% and 53.7%) followed by Klebsiella spp. (11.5% and 21.9%) in IAIs and UTIs, respectively. Figures for Pseudomonas aeruginosa were 9.0% and 6.1%, being more frequently recovered from patients with nosocomial infections. Overall, 9.9% (IAI) and 14.0% (UTI) of E. coli, Klebsiella spp. and Proteus mirabilis isolates were ESBL-producers, being Klebsiella pneumoniae (34.5%) from UTI of nosocomial origin the most frequent. ESBL-producers were higher in patients >60 years in both IAIs and UTIs. As in previous years, amikacin (96.3%-100% susceptibility), ertapenem (84.2%-100%) and imipenem (70.3%- 100%) were the most active antimicrobials tested among Enterobacterales species. The activity of amoxicillin-clavulanic, piperacillin-tazobactam, and ciprofloxacin susceptibility was lower, particularly among ESBL-producers. Ertapenem susceptibility (88.9%-100%) was retained in ESBL-E. coli isolates that were resistant to these antimicrobials but decreased (28.6%-100%) in similar isolates of K. pneumoniae.
Conclusions. Continuous antimicrobial resistance surveillance from the SMART study reveals overall maintenance of ESBL-producers in Spain, although with higher presence in isolates from UTIs than from IAIs. Moreover, ertapenem activity was high in E. coli irrespective of ESBL production but decreased in K. pneumoniae, particularly among ESBL-producers.

Rev Esp Quimioter 2019; 32(2): 145-155 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(2): 137-144

Effectiveness and safety of daclatasvir/sofosbuvir with or without ribavirin in genotype 3 hepatitis C virus infected patients. Results in real clinical practice

LUIS MARGUSINO-FRAMIÑÁN, PURIFICACIÓN CID-SILVA, ÁLVARO MENA-DE-CEA, IRIA RODRÍGUEZ-OSORIO, BERTA PERNAS-SOUTO, MANUEL DELGADO-BLANCO, SONIA PERTEGA-DÍAZ, ISABEL MARTÍN-HERRANZ, ÁNGELES CASTRO-IGLESIAS

Objectives. Direct-acting antivirals have shown high efficacy in all hepatitis C virus (HCV) genotypes, but genotype 3 (G3) treatments continue to be a challenge, mainly in cirrhotic patients. The aim of this study is to analyse effectiveness and safety of daclatasvir associated with sofosbuvir with or without ribavirin in G3-HCV infected patients in real clinical practice.
Patients and methods. An observational, prospective, cohort study over 2.5 years, in G3-HCV infected adult patients, in all fibrosis stages including patients with decompensated cirrhosis. Treatment was a combination of sofosbuvir 400 mg/day + daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events.
Results. A total of 111 patients were enrolled, 32.4% cirrhotics and 29.9% treatment-experienced. The global SVR12 rate was 94.6%, while the SVR12 rate in F3-4 fibrosis stage patients was 90.8% versus 100% in patients with F0-2 fibrosis (p=0.03). In cirrhotic patients, SVR12 was 100% versus 40% depending on whether ribavirin was added or not to daclatasvir/sofosbuvir (p=0.001). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed.
Conclusions. Daclatasvir/sofosbuvir ± ribavirin is highly effective in G3-HCV infected patients. Advanced degrees of fibrosis significantly decrease the effectiveness of this treatment, which motivates the need for the addition of ribavirin in cirrhotic patients. The regimen was safe and well tolerated.

Rev Esp Quimioter 2019; 32(2): 137-144 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(2): 130-136

Efficacy of an information system addressed to nursing staff for diminishing contaminated blood cultures: a blind clinical trial

MIGUEL CERVERO, SARA QUEVEDO, MANUEL DEL ÁLAMO, PABLO DEL VALLE, ISABEL WILHELMI, RAFAEL TORRES, JOSE LUIS AGUD, VICTORIA ALCÁZAR, SHEILLA VÁZQUEZ, BEATRIZ GARCÍA

Introduction. Evaluate the efficacy of an information system addressed to nursing staff to lower the blood culture contamination rate.
Methods. A blind clinical trial was conducted at Internal Medicine and Emergency Departments during 2011. After following a reeducation program in BC extraction, participants were randomly selected in a 1:1 ratio. Every participant of the experimental group was informed of each worker’s individual performance; whereas the control group was only informed of the global results.
Results. A total of 977 blood extractions were performed in 12 months. Blood culture contamination rate was 7.5%. This rate was higher in the Emergency Department than in Internal Medicine (10% vs. 3.8%; p=0.001). Factors associated with the higher risk of contamination were, in the univariate analysis, the extraction through a recently implanted blood route and the time of professional experience, while those associated with a lower risk were the extraction in Internal Medicine and through a butterfly needle. On multivariate analysis, extraction through a recently placed access was an independent risk factor for an increased contamination rate (OR 2.29; 95%CI 1.18-4.44, p=0.014), while individual information about the blood culture results (OR 0.11; 95%CI 0.023-0.57; p=0.008), and more than 9 years of professional experience were asso-ciated with fewer contaminations (OR 0.30; 95%CI 0.12-0.77; p=0.012). In the intervention group the contamination rate diminished by a 26 %.
Conclusions. Drawing blood cultures through a recently taken peripheral venous access increased their risk of contamination. The intervention informing the nurse staff of the contamination rate is effective to decrease it.

Rev Esp Quimioter 2019; 32(2): 130-136 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(2): 121-129

Application of pharmacokinetic/pharmacodynamic analysis to evaluate the adequacy of antimicrobial therapy for pediatric acute otitis media in Spain before and after the introduction of the PCV7 vaccine

MAITANE IBAR-BARIAIN, ALICIA RODRÍGUEZ-GASCÓN, ARANTXA ISLA, MARÍA ÁNGELES SOLINÍS, ANDRÉS CANUT-BLASCO

Objectives. To evaluate, by applying pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the change in antibiotic susceptibility after the introduction of the 7-valent pneumo-coccal conjugate vaccine (PCV7) in Spain had any influence on the usefulness of the antimicrobials more frequently used as empirical treatment of pediatric acute otitis media (AOM).
Material and methods. PK parameters and susceptibility of Streptococcus pneumoniae and Haemophilus influenzae were obtained from bibliography. Monte Carlo simulation was used to estimate the cumulative fraction of response (CFR), understood as the expected probability of therapy success. For amoxicillin and amoxicillin/clavulanate, the target was free antibiotic concentration remaining above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval (fT>MIC≥50%), whereas for cefuroxime axetil and cefotaxime, the target was fT>MIC≥60%. CFR values ≥90% were considered successful.
Results. When all serotypes of S. pneumoniae are considered, amoxicillin and cefotaxime turned out to reach a high probability of success, and difference before and after vaccination was scarce. For H. influenzae, CFR values were higher with amoxicillin/clavulanate than with amoxicillin. For both microorganisms, cefuroxime axetil resulted in low probability of success in the two periods of study.
Conclusions. We have shown that the introduction of the PCV7 vaccination did not lead to changes in the probability of success of the current empiric treatments of the AOM. Integrated PK/PD analysis has demonstrated to be a useful tool to identify changes in antimicrobial activity after the implantation of a vaccination program, providing complementary information to the simple assessment of MIC values.

Rev Esp Quimioter 2019; 32(2): 121-129 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(2): 114-120

Typing and antimicrobial susceptibility of 134 Neisseria gonorrhoeae strains from Southern Spain

FERNANDO COBO, M. TERESA CABEZAS-FERNÁNDEZ, CRISTÓBAL AVIVAR

Introduction. Last guidelines have recommended the introduction of dual antimicrobial therapy in order to avoid treatment failure. In the present report, the susceptibility to some antibiotics was evaluated, and the typing of Neisseria gonorrhoeae strains was performed.
Material and methods. Gonococcal isolates were tested for susceptibility according to the recommendations of both CLSI and EUCAST. A total of 134 isolates were typed by the NG-MAST technique.
Results. Seventy-two different N. gonorrhoeae types were found, and the most frequent types obtained were ST 1407, ST 14958, ST 7192, ST 13251 and ST 5405. If CLSI/EUCAST criteria were applied, a ST 9807 type was found nonsusceptible to ceftriaxone and cefixime (MIC 0.5 mg/L), and a ST 12800 type was found nonsusceptible only to cefixime (MIC 0.25 mg/L). When only EUCAST breakpoints were taken into account, three strains were also resistant to cefixime (MIC 0.25 mg/L) and three isolates were resistant to ceftriaxone (MIC 0.19, 0.16 and 0.25 mg/L, respectively). The majority of strains were resistant to ciprofloxacin (68.6%), and all N. gonorrhoeae strains were susceptible to spectinomycin; 9.7% of isolates were resistant to azithromycin.
Conclusions. Molecular typing may be a useful tool to predict antimicrobial resistance. High rates of resistance to penicillin, tetracycline and ciprofloxacin were found in this area. It is highly recommended to carry out antimicrobial susceptibility in all gonorrhoea cases and to identify treatment failures to verify emerging resistance. 

Rev Esp Quimioter 2019; 32(2): 114-120 [Full-text PDF]

 

 

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Rev Esp Quimioter 2019; 32(1): 1-5

Baloxavir marboxil: a potent cap-dependent endonuclease inhibitor of influenza viruses

JORDI REINA, NURIA REINA

Baloxavir marboxil (5-hydroxy-4-pyridone-3-carboxyl acid) is a new antiviral drug with special efficacy on influenza viruses that acts by inhibiting the cap-dependent endonuclease required for its replication. It is the first representative of the so-called inhibitors of influenza-like PB2. It has shown efficacy against influenza viruses A and B and most strains of animal origin (avian flu). Clinical trials conducted in healthy patients between 12 and 64 years without pathologies and not hospitalized (mild flu) have shown a reduction in the duration of symptoms similar to that obtained by oseltamivir. However, baloxavir is a much more potent inhibitor of viral replication than this drug. It has been shown as a safe and well tolerated drug. A single dose of 40-80 mg is administered the first 48 hours after onset of symptoms. In these trials, strains with moderate sensitivity (PA / I38T mutants) were detected in 2.2% of influenza A (H1N1) pdm09 and in 9.7% of influenza A (H3N2). Although these data could be a good drug to treat mild or moderate influenza, requiring trials in severe influenza and patients with chronic diseases to establish their true clinical utility.

Rev Esp Quimioter 2019; 32(1): 1-5 [Texto completo PDF]

 

 

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Rev Esp Quimioter 2019; 32(1): 73-77

Economic evaluation of the Alfred 60/AST device implantation for bacterial growth detection with automatic sewing machine

OSCAR HERRÁEZ CARRERA, MARÍA HUERTAS VAQUERO, MARÍA ÁNGELES ASENCIO EGEA, JORGE GAITÁN PITERA, RAFAEL CARRANZA GONZÁLEZ

Introduction. It is becoming increasingly necessary to automatize screening of urine samples to culture at Microbiology laboratories. Our objective was to estimate the budget threshold from which the Alfred 60/AST device would be profitable for our hospital.
Material and methods. Cost minimization study by decision trees, carried out in a General Hospital. The cost of traditional urine culture and urine processing using Alfred-60/AST were compared. Traditional processing involves the culture of all urine specimens received onto blood and MacConkey agar, and identification of every microorganism isolated by Vitek-2 system. The autoanalyzer would only inoculate the positive urines onto a chromogenic media, directly identifying the Escherichia coli isolates.
Results. The variables with the greatest economic impact in the model were the probability of obtaining a positive culture, the prevalence of E. coli in the urine cultures and the cost per sample using Alfred-60/AST. The multivariate sensitivity analysis showed that the model was solid. The bivariate sensitivity analysis showed that the model is suceptible to cost modification, mainly of the automatic device. At a threshold value of 1.40 euros/determination, the automatic processing would decrease the annual costs in 2,879 euros.
Conclusion. The introduction of the Alfred-60/AST device in our laboratory at 1.40 euros/determination would reduce urine processing workload, saving time and costs.

Rev Esp Quimioter 2019; 32(1): 73-77  [Texto completo PDF]

 

 

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Rev Esp Quimioter 2019; 32(1): 22-30

Factors associated with development of nephrotoxicity in patients treated with vancomycin versus daptomycin for severe Gram-positive infections: A practice-based study

JOSÉ BARBERÁN, JOSÉ MENSA, ARTURO ARTERO, FRANCISCO EPELDE, JUAN-CARLOS RODRIGUEZ, JOSEFA RUIZ-MORALES, JOSÉ-LUIS CALLEJA, JOSÉ-MANUEL GUERRA, IÑIGO MARTÍNEZ-GIL, MARÍA-JOSÉ GIMÉNEZ, JUAN-JOSÉ GRANIZO, LORENZO AGUILAR

Objectives. To evaluate nephrotoxicity development in patients treated with vancomycin (VAN) and daptomycin (DAP) for proven severe Gram-positive infections in daily practice.
Patients and methods. A practice-based, observational, retrospective study (eight Spanish hospitals) was performed including patients ≥18 years with a baseline glomerular filtration rate (GFR)>30 mL/min and/or serum creatinine level<2 mg/dL treated with DAP or VAN for >48h. Nephrotoxicity was considered as a decrease in baseline GRF to <50 mL/min or decrease of >10 mL/min from a baseline GRF<50 mL/min. Multivariate analyses were performed to determine factors associated with 1) treatment selection, 2) nephrotoxicity development, and 3) nephrotoxicity development within each antibiotic group.
Results. A total of 133 patients (62 treated with DAP, 71 with VAN) were included. Twenty-one (15.8%) developed nephrotoxicity: 4/62 (6.3%) patients with DAP and 17/71 (23.3%) with VAN (p=0.006). No differences in concomitant administration of aminoglycosides or other potential nephrotoxic drugs were found between groups. Factors associated with DAP treatment were diabetes mellitus with organ lesion (OR=7.81, 95%CI:1.39-4.35) and basal creatinine ≥0.9 mg/dL (OR=2.53, 95%CI:1.15-4.35). Factors associated with VAN treatment were stroke (OR=7.22, 95%CI:1.50-34.67), acute myocardial infarction (OR=6.59, 95%CI:1.51-28.69) and primary bacteremia (OR=5.18, 95%CI:1.03-25.99). Factors associated with nephrotoxicity (R2=0.142; p=0.001) were creatinine clearance<80 mL/min (OR=9.22, 95%CI:1.98-30.93) and VAN treatment (OR=6.07, 95%CI:1.86-19.93). Factors associated with nephrotoxicity within patients treated with VAN (R2=0.232; p=0.018) were congestive heart failure (OR=4.35, 95%CI:1.23-15.37), endocarditis (OR=7.63, 95%CI:1.02-57.31) and basal creatinine clearance<80 mL/min (OR=7.73, 95%CI:1.20-49.71).
Conclusions. Nephrotoxicity with VAN was significantly higher than with DAP despite poorer basal renal status in the DAP group.

Rev Esp Quimioter 2019; 32(1): 22-30  [Full-text PDF]

 

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Rev Esp Quimioter 2019; 32(1): 40-49

Influence of pharmacist intervention, based on CMO model, to improve activation in HIV patients

RAMÓN MORILLO-VERDUGO, Mª DE LAS AGUAS ROBUSTILLO-CORTÉS, MERCEDES MANZANO GARCÍA, CARMEN VICTORIA ALMEIDA-GONZÁLEZ

Objectives. The aim of study was to evaluate the influence of pharmacist intervention based on “CMO model”, to improve activation in HIV-patients.
Material and methods. Longitudinal, prospective, single-center study. Eligible patients were HIV-infected, taking antiretroviral treatment. The collected data included demographic characteristics, clinical and HIV-related and pharmacotherapeutic variables. The primary outcome was the variation of patient activation measured by Spanish adapted patient activation measure questionnaire. This questionnaire assesses people’s knowledge, skills and confidence in managing their own health care. The assessment was performed at the beginning and 6 months after the program start, which consisted of individualized interventions planned in the stratification model, a motivational interview and a specific pharmacotherapeutic follow-up.
Results. A total of 140 patients were included. The most common regimens prescribed were based on non-nucleoside plus nucleoside reverse transcriptase inhibitor (44.0%) and more than half of the patients had chronic concomitant medication. The patients who achieved the highest activation level increased from 28.1% to 68.3% (p<0.0005). The relationship between this increase in patient activation and the stratification level that occurs in largest increases in patients with a low need level, where it was observed an improvement in the percentage of patients with high activation from 28.3% to 74.3% (p<0.001) after intervention. The percentage of patients with adequate adherence to concomitant treatment increased by 18.4% (p = 0.035). Baseline PAM values showed high activation for 28.6% (40 patients), intermediate for 43.6% (61) and low for 27.9% (39).
Conclusion. CMO model has an important role for patient activation, improving adherence and health outcomes for HIV+ patients.

Rev Esp Quimioter 2019; 32(1): 40-49  [Full-text PDF]

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