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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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Rev Esp Quimioter 2019; 32(1): 68-72

Antimicrobial activity of ceftolozane-tazobactam against multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa clinical isolates from a Spanish hospital

ANA ISABEL LÓPEZ-CALLEJA, ELENA MORILLA MORALES, ROSSI NUÑEZ MEDINA, MARTA FERNÁNDEZ ESGUEVA, JUAN SAHAGÚN PAREJA, JUAN MANUEL GARCÍA-LECHUZ MOYA, ISABEL FERRER CERÓN, JESÚS VIÑUELAS BAYON, ANTONIO REZUSTA LÓPEZ

Objectives. Our objective was to evaluate the in vitro activity of ceftolozane-tazobactam against multidrug resistant (MDR) and extensively drug-resistant (XDR) non metallo-β-lactamase producing Pseudomonas aeruginosa clinical isolates at Hospital Universitario Miguel Servet (Zaragoza, Spain) from February 2016 to October 2017.
Material and methods. We evaluated the in vitro activity of ceftolozane-tazobactam and other antipseudomonal antibiotics against 12 MDR and 117 XDR non metallo-β-lactamase producing P. aeruginosa isolates. Ceftolozane-tazobactam minimal inhibitory concentrations (MICs) were determined by MIC gradient diffusion test strip.
Results. Among the 129 MDR/XDR isolates included, 119 (92.2%) were susceptible to ceftolozane-tazobactam, and ten (7.8%) were resistant. MIC50 was 2 mg/L, and MIC90 4 mg/L. Ceftolozane-tazobactam was the second most active antibiotic after colistin, overtaking amikacin.
Conclusions. Ceftolozane-tazobactam is a valuable treatment option for MDR and XDR P. aeruginosa infections in our setting.

Rev Esp Quimioter 2019; 32(1): 68-72  [Full-text PDF]

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Rev Esp Quimioter 2019; 32(1): 60-67

Evolution of the incidence of colonized and infected patients by VIM carbapenemase-producing bacteria in a pediatric hospital in Spain

RAQUEL GONZÁLEZ-RUBIO, DAVID PARRA-BLÁZQUEZ, ISABEL SAN-JUAN-SANZ, GUILLERMO RUIZ-CARRASCOSO, SARA GALLEGO, LUIS ESCOSA-GARCÍA, ANA ROBUSTILLO-RODELA

Introduction. The aim of this study is to describe the evolution of the incidence of infected and colonized patients with carbapenemase VIM-producing bacteria (CPB-VIM) at a national referral pediatric center in Madrid, Spain, between 2012 and 2015.
Material and methods. Descriptive epidemiological surveillance study. The surveillance system included case detection (screening for BPC colonization in all admitted patients, with periodicity according to the ward) and control measures (contact precautions, identification of previously colonized patients at admission, environmental cleaning, education, supervision of contact precautions, and patient cohort). All hospitalized patients with first positive microbiological sample for CPB-VIM in 2012-2015 were included. Colonized patients were followed through clinical history to evaluate later infection.
Results. We found 239 colonized and 51 infected patients with CPB-VIM (49.3% women, 47.6% were 5 months old or younger, 52.1% admitted at Intensive Care Unit). Infection and colonization incidence were, respectively, 2.6 and 6.7 cases per one thousand hospitalized patients in 2012, 1.8 and 10.0 in 2014 and 0.3 and 5.0 in 2015. Within these patients, 84.4% shared ward with other patient with previous positive sample. 13.0% (31/239) of colonized patients had a subsequent infection.
Conclusions. We have shown data of pediatric patients affected by BPC-VIM, collected from an epidemiological surveillance system that included systematic screening at a national referral center. After an epidemic period, the incidence of cases went down. The surveillance and infection control measures intensification, as well as coordination with involved departments, were key in the handling of the situation.

Rev Esp Quimioter 2019; 32(1): 60-67  [Texto completo PDF]

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Rev Esp Quimioter 2019;32(1): 31-39

Strategies for the management of invasive fungal infections due to filamentous fungi in high-risk hemato-oncological patients

CARLOS VALLEJO, JESÚS FORTÚN AND THE STUDY GROUP FOR IFI MANAGEMENT

Introduction. In recent years, the introduction of new antifungals for the prevention of invasive fungal infections (IFIs) in hemato- oncological patients, particularly extended-spectrum azoles, has led to a change in the diagnostic and therapeutic strategies for established or suspected breakthrough IFI. The aim of the study was to identify the diagnostic and therapeutic strategies used in the management of IFIs in hemato-oncological patients in Spain, and to assess compliance with the recommendations of the consensus documents and clinical practice guidelines.
Patients and Methods. An online, anonymous, cross-sectional survey was conducted between January and September 2016 involving 137 specialists from third-level hospitals in Spain with Departments of Hematology that regularly deal with IFIs.
Results. Galactomannan test was available to 95.6% of specialists, and was used in 61.7% of the cases for diagnostic confirmation and early treatment. The (1 → 3) β-D-glucan test was only available to 10.2%. A total of 75.3% of the participants estimated the incidence of breakthrough IFI due to filamentous fungus as being 1-10%. In turn, 83.3% of the participants decided a change in antifungal class after failure of prophylaxis, in concordance with the recommendations of the national and international consensus documents.
Conclusions. The present study, the first of its kind conducted in Spain, shows that a high percentage of the medical professionals implicated in the management of hemato-oncological patients at high risk of suffering IFIs follow the recommendations of the national and international consensus documents and guidelines.

Rev Esp Quimioter 2019;32(1): 31-39  [Full-text PDF]

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Rev Esp Quimioter 2019; 32(1): 50-59

Recommendations from a panel of experts on the usefulness of fidaxomicin for the treatment of infections caused by Clostridium difficile

EMILIO BOUZA, JAVIER COBO, BENITO ALMIRANTE Y EL GRUPO DE TRABAJO CLODIEXPAN

Introduction. Clostridium difficile infections have a high recurrence rate, which can complicate the prognosis of affected patients. It is therefore important to establish an early detection and an appropriate therapeutic strategy. The objective of this manuscript was to gather the opinion of an expert group about the predictive factors of poor progression, as well as when to use fidaxomicin in different groups of high-risk patients.
Methods. A scientific committee of three experts in infectious diseases reviewed the most recent literature on the management of C. difficile infections, and the use of fidaxomicin. They developed a questionnaire of 23 items for consensus by 15 specialists in this type of infection using a modified Delphi method.
Results. The consensus reached by the panelists was 91.3% in terms of agreement. The most important agreements were: recurrence is a risk criterion per se; fidaxomicin is effective and safe for the treatment of infections caused by C. difficile in critical patients, immunosuppressed patients, or patients with chronic renal failure; fidaxomicin is recommended from the first episode of infection to ensure maximum efficacy in patients with well-contrasted recurrence risk factors.
Conclusions. The experts consulted showed a high degree of agreement on topics related to the selection of patients with poorer prognosis, as well as on the use of fidaxomicin in groups of high-risk patients, either in the first line or in situations of recurrence.

Rev Esp Quimioter 2019; 32(1): 50-59  [Texto completo PDF]

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Rev Esp Quimioter 2019; 32(1): 15-21

Bacteremia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. A retrospective study of 7 years

MARÍA INÉS LESPADA, EZEQUIEL CÓRDOVA, VIRGINIA ROCA, NORA GÓMEZ, MARCELA BADÍA, CLAUDIA RODRÍGUEZ

Introduction. Bacteremia caused by Klebsiella pneumoniae carbapenemase-producing strains (Kp-KPC) is associated with high mortality. The hypothesis of our work is that there was an increase in the levels of resistance to different antimicrobials in Kp-KPC isolated from bacteremia
Materials and methods. Retrospective and descriptive study in two periods: Period 1 (P1) 2010-2014 and period 2 (P2) 2015-2016. We included patients ≥18 years old with bacteremia caused by Kp-KPC in a General Hospital. We defined active drug (AD) if it was in vitro susceptible and in the case of meropenem if it had a MIC ≤ 8 mg/L in combination treatment.
Results. Fifty episodes of bacteremia caused by Kp-KPC were analyzed in 45 patients. (P1: 21 and P2: 29). The following variables were similar in both periods: median age (53 vs. 52 years); male sex (45 vs. 62%); site of infection: primary bacteremia (52 vs.45%), bacteremia associated with catheter (24 vs.17%), and other (24 vs. 38%). During P2 there was a significant increase in colistin resistance (28 vs. 69%) (p <0.01), an increase in MIC to meropenem ≥ 16 mg/L (74 and 97%) (p = 0.02), and decrease in tigecycline resistance (29 vs. 4%) (p = 0.02). The overall mortality was 40 in P1 and 32% in P2 (p=0.7). There was not difference in mortality when the definitive treatment was with an active antimicrobial vs. two active antimicrobials, as well as between the different antimicrobials used.
Conclusions. There was a significant increase in bacteremia caused by Kp-KPC and the level of colistin resistance and MIC to meropenem. Overall mortality was high in both periods.

Rev Esp Quimioter 2019; 32(1): 15-21  [Texto completo PDF]

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Rev Esp Quimioter 2019; 32(1): 6-14

Impact of empirical treatment with antifungal agents on survival of patients with candidemia

RODRIGO POVES-ALVAREZ, BEATRIZ CANO-HERNÁNDEZ, MARÍA FE MUÑOZ-MORENO, SARA BALBÁS-ALVAREZ, PATRICIA ROMÁN-GARCÍA, ESTHER GÓMEZ-SÁNCHEZ, BEATRIZ MARTÍNEZ-RAFAEL, ESTEFANÍA GÓMEZ-PESQUERA, MARIO LORENZO-LÓPEZ, ELISA ALVAREZ-FUENTE, OLGA DE LA VARGA, MIGUEL FLORES, JOSÉ MARÍA EIROS, EDUARDOTAMAYO, MARÍA HEREDIA-RODRÍGUEZ

Introduction. The objective of this study was to evaluate the impact of echinocandins and fluconazole) on mortality 7 and 30 days after candidemia onset and overall in-hospital mortality), in patients with candidemia at a Spanish tertiary hospital.
Methods. A retrospective study was conducted that enrolled all non-neutropenic adult patients diagnosed with candidemia at Hospital Clínico Universitario de Valladolid between 2007 and 2016. A total of 179 patients were evaluated, they were divided into two sub-groups: surviving patients (n = 92) and non-surviving patients (n = 87).
Results. The 7-day mortality was 25,1% (45), 30-day mortality was 46,9% (84), and overall in-hospital mortality was 48,6% (87). 40.8% of patients received no antifungal treatment (43.8% of surviving patients and 37.8% of non-surviving patients; p=0.15). A total of 106 (59.2%) patients were treated, of which 90 patients (50.3%) received empiric treatment. 19.6% and 47.8% of surviving patients were treated with echinocandins and fluconazole, respectively. By contrast, of non-surviving patients, 31.0% were treated with echinocandins and 47.1% received fluconazole. Survival for the first 7 days was significantly higher in treated with antifungal agents (log-rank = 0.029), however, there were not significant differences in 30-day survival. Factors linked to a significant increase in overall in-hospital mortality were age (OR 1.040), septic shock (OR 2.694) and need for mechanical ventilation > 48 h (OR 2.812).
Conclusion. Patients who received antifungal treatment, regardless of whether they received fluconazole or echinocandins, had a significantly lower mortality rate after 7 days than untreated patients, although no significant differences in 30-day mortality were seen.

Rev Esp Quimioter 2019; 32(1): 6-14  [Full-text PDF]

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Rev Esp Quimioter 2018; 31(6): 485-492.

Evolution of treatment of syphilis through history

CRISTINA ROS-VIVANCOS, MARÍA GONZÁLEZ-HERNÁNDEZ, JUAN FRANCISCO NAVARRO-GRACIA, JOSÉ SÁNCHEZ-PAYÁ,  ANTONIO GONZÁLEZ-TORGA, JOAQUÍN PORTILLA-SOGORB

In this article, we present a historical revision of syphilis treatment since the end of the XV century up until the current days. For centuries, it was understood that syphilis had been brought to Spain by Columbus after coming back from America. It became an epidemic soon after. Later on, it was spread all over Europe. The chronologic and geographic origin of this illness have been debated in recent years, however, there has been no agreement about it as yet. Mercury was the main used therapy for four and a half centuries, until the discovery of penicillin in 1943. This discovery changed the therapeutic approach to syphilis since then. Other remedies were used during this period. Guaiacum was one of them, but it was dismissed in the mid-sixteenth century. Iodides were also used, especially in the tertiary symptoms of the disease. The discovery of arsphenamine (Salvarsan) at the beginning of the XX century, used by itself at its onset and associated to mercury or bismuth later on, was a significant therapeutic contribution. Bismuth was in itself a great therapeutic asset. It displaced the use of mercury in an important way until 1943, when the appearance of penicillin became the treatment of choice.

Rev Esp Quimioter 2018; 31(6): 485-492.  [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(6): 542-545

Interleukin (IL) -1 β, IL-6 and tumor necrosis factor in patients with seasonal flu

JOSÉ M. RAMOS, MAR GARCÍA-NAVARRO, VICTORIA MORENO, PILAR GONZÁLEZ-DE-LA-ALEJA, ADELINA GIMENO-GASCÓN, ESPERANZA MERINO, JOAQUÍN PORTILLA

Introduction. The role of tumor necrosis factor (TNF), interleukin (IL)-1β and IL-6 in the pathogenicity of seasonal flu is unknown.
Methods. We analyzed the profiles of these cytokines in 77 flu patients and 17 controls with non-flu respiratory infection, using molecular biology techniques (real-time polymerase chain reaction).
Results. Flu patients had lower monocyte counts (p=0.029) and a slightly lower median level of IL-6 (P=0.05) than the control group. Twenty-four flu patients (31.2%) had pneumonia; this group had higher C-reactive proteins (p=0.01) and monocyte levels (p=0.009). Pro-inflammatory cytokines levels did not rise in patients with pneumonia complicating seasonal influenza
Conclusion. IL-6 levels were lower in adults with influenza.

Rev Esp Quimioter 2018; 31(6): 542-545  [Full-text PDF]

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