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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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Rev Esp Quimioter 2018; 31(6): 520-527

Utilisation of first-line antibiotics six years after a multifaceted intervention

JOSÉ M. MOLERO, MANUEL GÓMEZ, GLORIA GUERRA, JUAN DE DIOS ALCÁNTARA, JESÚS ORTEGA, GUILLERMO GARCÍA, VICENTA PINEDA, SUSANA MUNUERA, MARINA CID, M. JOSÉ MONEDERO, JOANA M. RIBAS, JOSEP M. COTS, ANA MORAGAS, LARS BJERRUM, CARLES LLOR, GRUPO DE TRABAJO HAPPY AUDIT 3

Introduction. No study has evaluated the impact of a multifaceted intervention on the quality of the antibiotics prescribed more than 5 years later.
Material and methods. A total of 210 general practitioners (GP) from eight different regions of Spain were asked to participate in two registrations of respiratory tract infections (RTI) in 2008, before, and in 2009, just after a multifaceted intervention including prescriber feedback, clinical guidelines, training sessions focused on appropriate antibiotic prescribing, workshop on rapid tests and provision of these tests in the GP consultation. They were all again invited to participate in a similar registration in 2015. A new group of clinicians from the same areas who had never participated in antimicrobial stewardship courses were also invited to participate and acted as controls.
Results. The 121 GPs who continued the study (57.6%) and the 117 control GPs registered 22,407 RTIs. The antibiotic most commonly prescribed was amoxicillin and clavulanic acid, prescribed in 1,801 cases (8.1% of the total), followed by amoxicillin (1,372 prescriptions, 6.2%), being lower among GPs just after the intervention. The third leading antibiotic among GPs just after the intervention was penicillin V (127 cases, 3.3%) whereas macrolides ranked third in the other three groups of GPs.
Conclusions. The use of first-line antibiotic for RTIs wanes over time after an intervention, but their utilisation is still significantly greater among intervened clinicians six years later compared to GPs who have never been exposed to any antimicrobial stewardship programmes.

Rev Esp Quimioter 2018; 31(6): 520-527  [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(6): 511-519

Description of Influenza B in seasonal epidemics in Spain

RAÚL ORTIZ DE LEJARAZU, JAVIER DÍEZ DOMINGO, ÁNGEL GIL DE MIGUEL, FEDERICO MARTINÓN TORRES, CARLOS GUZMÁN QUILO, JOSÉ MARÍA GUILLÉN, BLANCA PIEDRAFITA, ESTHER REDONDO MARGUELLO

Introduction. Seasonal influenza epidemics are a major public health concern. They are caused by the influenza A and B viruses; although the A virus is more prominent, influenza B virus infection causes a disease with similar characteristics. There are two phylogenetically distinct influenza B lineages (B/Victoria and B/Yamagata), only one of which is present in the trivalent vaccine formulated each season.
Methods. Epidemiological data from the Spanish Influenza Surveillance System for 2007 to 2017 were reviewed to establish the relative proportion of each type of virus and the characterization of the B lineages in relation to the composition of the trivalent vaccine.
Results. The median proportion of B (2007-2017) was 27.2% (0.7%-74.8%) vs. 16.3% (0.4%-98.6%) for A-H3 and 44.2% (0.1%-98.0%) for pandemic A-H1N1 (20092017). The B lineages co-circulated in 8/10 seasons and there was mismatch with the B vaccine strain in 4/10 seasons. The B virus was dominant in 2007/08 and 2012/13 throughout Spain. There was a combination of dominance/codominance of influenza B and mismatch with the vaccine lineage in at least one third of epidemic seasons reviewed.
Conclusions. Epidemiological information on influenza B has been less compiled in comparison with data on the A virus. Influenza virus type B is responsible for a significant number of cases in almost all seasons. The predominant B lineage in each season is unpredictable, affecting the protection conferred by the seasonal vaccine. Spanish epidemiological data support the rationale for a quadrivalent vaccine with both B virus lineages similarly to data from other settings.

Rev Esp Quimioter 2018; 31(6): 511-519  [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(6): 494-505

Infectious postoperative endophthalmitis after cataract surgery performed over 7 years. The role of azithromycin versus ciprofloxacin eye drops

JOSEP TUÑÍ-PICADO, ANA MARTÍNEZ-PALMER, XÈNIA FERNÁNDEZ-SALA, JAIME BARCELÓ-VIDAL, MIGUEL CASTILLA-MARTÍ, YASMIN CARTAGENA-GUARDADO, SANTIAGO GRAU

Introduction. Although topical antibiotics have been used as antimicrobial prophylaxis after ocular surgery, recent studies have determined that intracameral cefuroxime at the end of surgery significantly reduce the risk to suffer an infection and suggest that the use of topical antibiotics in the prophylaxis of infectious postoperative endophthalmitis (IPOE) is controversial. Moreover, there is no evidence to confirm the higher effectiveness of topical ciprofloxacin, considered the standard of care, or topical azithromycin in preventing IPOE of cataract surgeries.
Patients and methods. IPOE topical prophylaxis was performed with two different strategies: with azithromycin from January 1st, 2010 to December 31st, 2014 (group I) and with ciprofloxacin from January 1st, 2015 to January 31st, 2017 (group II). Patient characteristics and clinical signs and symptoms of IPOE from all consecutive cataract surgeries performed over a 7-year period were collected.
Results. A total of 15,146 cataract surgeries were conducted; 10,756 in group I and 4,390 in group II. Two cases of IPOE in each group were diagnosed, showing a 0.019% and 0.046% rate respectively, with no statistically significance. IPOE cases were related with aging, systemic and ocular comorbidities or with a complicated cataract surgery.
Conclusions. The benefit of the application of topical antibiotics after cataract surgery is questionable when intracameral cefuroxime prophylaxis is performed and no better effectiveness with ciprofloxacin or azithromycin was observed.

Rev Esp Quimioter 2018; 31(6): 494-505  [Full-text PDF]

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Rev Esp Quimioter 2018; 31(6): 493-498

CD64 index as a marker of infection in patients with postoperative fever

NATALIA VICENTE LÓPEZ, RAFAEL FORÉS CACHÓN, REYES IRANZO VALERO, ANA LERMA VERDEJO, ELENA MÚÑEZ RUBIO, ANA ROYUELA VICENTE, ANTONIO RAMOS MARTÍNEZ

Objective. To evaluate the utility of the granulocyte CD64 index as a marker of infection in patients with postoperative fever.
Methods. Prospective observational study of a cohort of patients with postoperative fever (2nd-21st day after the intervention) collected during 14 months. Obtaining blood samples during the first 24 hours after the febrile peak to determine the CD64 index (ratio of fluorescence intensity, measured, in the granulocytes of the patient with respect to healthy controls), procalcitonin and C-reactive protein (CRP).
Results. During the study period, 50 patients were included, 28 patients (56%) with infection and 22 patients (44%) without evidence of infection. The PCR, procalcitonin and the CD64 index showed significantly higher values in the group of patients who suffered infection. The CD64 index showed a sensitivity of 88.9%, with a specificity of 65.2%. The positive predictive value (PPV) was 75% and the negative predictive value (NPV) was 83.3%, with an area under the curve (AUC) of 0.805 (95% CI 0.68-0.93). Procalcitonin presented a sensitivity of 53.9% and specificity of 86.4%, with NPV and PPV of 82.4% and 61.3% respectively, with AUC of 0.752 (95% CI 0.61-0.89). Regarding the PCR, it showed a sensitivity of 100%, with specificity of 4.4% with an area under the curve of 0.676 (95% CI 0.52-0.83).
Conclusions. The quantification of the CD64 index in patients who develop fever in the early postoperative period is useful to distinguish post-surgical inflammatory phenomena from episodes of established infection.

Rev Esp Quimioter 2018; 31(6): 493-498.  [Texto completo PDF]

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