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Rev Esp Quimioter 2018; 31(2): 136-145

Antimicrobial susceptibility trends and evolution of isolates with extended spectrum β-lactamases among Gram-negative organisms recovered during the SMART study in Spain (2011-2015)

RAFAEL CANTÓN, ELENA LOZA, JAVIER AZNAR, RUBÉN BARRÓN-ADÚRIZ, JORGE CALVO, F. JAVIER CASTILLO, EMILIA CERCENADO, RAMÓN CISTERNA, FERNANDO GONZÁLEZ-ROMO, JOSÉ LUIS LÓPEZ-HONTANGAS, ANA ISABEL SUÁREZ-BARRENECHEA, FE TUBAU, BRIAN MOLLOY, DIEGO LÓPEZ-MENDOZA, AND SMART-SPAIN WORKING GROUP

Introduction. The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study monitors antimicrobial susceptibility and extended spectrum β-lactamases (ESBLs) in Gram-negative bacilli recovered from intra-abdominal infections (IAI).
Material and methods. Antimicrobial susceptibility of 5,343 isolates from IAI recovered in 11 centres during the 2011-2015 SMART-Spain program was analysed by standard microdilution (EUCAST criteria) and compared with that from 2002-2010. ESBLs were phenotypically detected.
Results. Escherichia coli, the most common isolate, significantly decreased in community acquired IAI (60.9% 2002-2010 vs. 56.1% 2011-2015, P=0.0003). It was followed in prevalence by Klebsiella pneumoniae that increased both in the community (8.9% vs. 10.8%, P=0.016) and nosocomial (9.2% vs. 10.8%, P=0.029) IAI and P. aeruginosa, which significantly increased in community acquired IAI (5.6% vs. 8.0%, P=0.0003). ESBLs were more prevalent in K. pneumoniae (16.3%) than in E. coli (9.5%) of nosocomial origin and were more frequently isolated from elderly patients (>60 years). Considering all Enterobacteriaceae, ertapenem (92.3-100%) and amikacin (95.5%-100%) were the most active antimicrobials. Ertapenem activity, unlike amoxicillin-clavulanate or piperacillin-tazobactam, remained virtually unchanged in ESBL (100%) and non-ESBL (98.8%) E. coli producers. Its activity decreased in ESBL-K. pneumoniae (74.7%) but was higher than that of amoxicillin-clavulanate (14.0%) and piperacillin-tazobactam (24.0%). Interestingly, ertapenem susceptibility was maintained in >60% of ESBL isolates that were resistant to amoxicillin-clavulanate, piperacillin-tazobactam or fluoroquinolones.
Conclusions. SMART-Spain results support current guidelines which include ertapenem as empiric treatment in mild-moderate community-acquired IAI, particularly with ESBL producers. These recommendations will need to be updated with the recently introduction of new antimicrobials.

Rev Esp Quimioter 2018; 31(2): 136-145.  [Full-text PDF]

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Rev Esp Quimioter 2018; 31(2): 110-117

Impact of an antimicrobial stewardship program on urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli

ERIKA ESTEVE-PALAU, SANTIAGO GRAU, SABINA HERRERA, LUISA SORLÍ, MILAGRO MONTERO, CONCHA SEGURA, XAVIER DURÁN, JUAN P. HORCAJADA

Objective.  To analyze the clinical and economic impact of an antimicrobial stewardship program (ASP) targeting urinary tract infections (UTI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli.
Methods. An observational retrospective study that included adults with a diagnosis of UTI caused by ESBL-producing E. coli admitted to a tertiary care hospital in Barcelona, Spain, between January 2014 and December 2015. The impact of the ASP was analyzed in terms of clinical and economic outcomes.
Results. A total of 222 patients met the inclusion criteria and an intervention was made by the ASP team in 104 cases (47%). ASP intervention was an independent variable related to clinical cure (p = 0.008). Other variables influencing clinical outcomes were the McCabe Jackson score (p = 0.005) and outpatient status (p < 0.001). The ASP interventions in this study had no economic impact.
Conclusion. Antimicrobial stewardship has a positive clinical impact on UTIs caused by ESBL-producing E. coli. Further prospective studies are needed to assess the economic impact of ASPs on UTI caused by ESBL-producing E. coli.

Rev Esp Quimioter 2018; 31(2): 110-117 [Full-text PDF]

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Rev Esp Quimioter 2018; 31(1): 78-100

Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy

JOSÉ MENSA, JOSÉ BARBERÁN, ALEX SORIANO, PEDRO LLINARES, FRANCESC MARCO, RAFAEL CANTÓN, GERMAN BOU, JUAN GONZÁLEZ DEL CASTILLO, EMILIO MASEDA, JOSÉ RAMÓN AZANZA, JUAN PASQUAU, CAROLINA GARCÍA-VIDAL, JOSÉ MARÍA REGUERA, DOLORES SOUSA, JOAQUÍN GÓMEZ, MIGUEL MONTEJO, MARCIO BORGES, ANTONIO TORRES, FRANCISCO ALVAREZ-LERMA, MIGUEL SALAVERT, RAFAEL ZARAGOZA, ANTONIO OLIVER

Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic β-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections.

Rev Esp Quimioter 2017; 31(1): 78-100 [Full-text PDF]


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Rev Esp Quimioter 2018; 31(1): 21-26

Prevalence and phylogenetic analysis of Chlamydia trachomatis in a population of women in Posadas, Misiones

GRACIELA BEATRIZ JORDÁ, SILVINA ELIZABETH HANKE, JOSÉ MANUEL RAMOS-RINCÓN, JESSICA MOSMANN, MARÍA LORENA LOPÉZ, ANDREA CAROLINA ENTROCASSI, CECILIA CUFFINI

Background. Chlamydia trachomatis is the most prevalent bacteria causing sexually transmitted infections. In women, this infection can cause cervicitis and urethritis, although it’s usually asymptomatic. The aim of this study was to investigate the prevalence of C. trachomatis in women attending the lab Instituto de Previsión Social and detect the genotypes.
Material and methods. Endocervical samples from 505 symptomatic and asymptomatic women were assayed. It was determined the presence of C. trachomatis by PCR through amplification of a fragment of the cryptic plasmid. Positive samples were genotyped by the partial amplification of the ompA gene and analyzed phylogenetically.
Results. Forty-three positive samples were detected to infection with C. trachomatis, obtaining a prevalence of 8.5% (IC 95%: 6.4-11.3%). The prevalence of C. trachomatis was higher in women with vaginal symptoms [11.3% (30/265) vs. 5.4% (13/240)] (p = 0.018), as well as in women under 26 year-old [11.5% (28/244) vs. 6.2% (15/246)] (p = 0.021). Based on phylogenetic analysis, it was observed that 62% of the samples were genotype E, 15% genotype J, 15% genotype D, and 8% genotype F.
Conclusions. This work is the first contribution on the molecular epidemiology of C. trachomatis in the Misiones province, Argentina, which shows the rate of prevalence of this bacterium and offers information on circulating genotypes.

Rev Esp Quimioter 2017; 31(1): 21-26 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(2):101-104

Phage therapy, an alternative to antibiotic therapy?

JORDI REINA, NURIA REINA

Bacteriophages are viruses that infect and parasitize bacteria. They can present a lytic cycle that determines the lysis of the infected bacteria. Each phage is specific to a particular bacterial genus or species.
The current increase in the incidence of antibiotic resistance in human bacteria has favored the study of phages as a therapeutic alternative (phage therapy). Previous studies have shown the efficacy of these elements in cutaneous and intestinal infections. Different clinical trials are underway to establish the safety, reactogenicity and therapeutic efficacy of multiple phage.
Being active elements, phages must undergo rigorous quality controls to ensure the absence of undesirable effects. The bacterial lysis that they cause is of a magnitude inferior to the one provoked by the antibiotics. As problems to be solved in the future are the possibility of using mixtures of several phages, establish the ideal route of administration and modify them genetically to deactivate bacterial resistance genes.

Rev Esp Quimioter 2017; 31(2):101-104 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(1): 1-12

Antibiotic diffusion to central nervous system

JOSÉ MARÍA CABRERA-MAQUEDA, LUNA FUENTES RUMÍ, GABRIEL VALERO LÓPEZ, ANA ESTHER BAIDEZ GUERRERO, ESTEFANÍA GARCÍA MOLINA, JOSÉ DÍAZ PÉREZ, ELISA GARCÍA-VÁZQUEZ

Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice.

Rev Esp Quimioter 2017; 31(1): 1-12 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(1): 35-42

Interferon-free treatments in patients with hepatitis C genotype 3 infection in a tertiary hospital

JUAN CARLOS DEL RIO-VALENCIA, ROCÍO ASENSI-DIEZ, RAQUEL MADERA-PAJIN, LUCÍA YUNQUERA-ROMERO, ISABEL MUÑOZ-CASTILLO

Introduction. Hepatitis C virus genotype 3 represents a unique entity within HCV treatment and multiple studies have documented that HCV genotype 3 infection is associated with more rapid disease progression than other genotypes, resulting in increased risk of cirrhosis, hepatocellular carcinoma, and all-cause mortality. In the current study, we further evaluated the real-world effectiveness of 12 weeks of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) and sofosbuvir + daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients infected with HCV genotype 3, with or without cirrhosis.
Material and methods. Retrospective and observational study carried out in a third level hospital. Study period: April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3 infection treated either with LDV/SOF ± RBV or with SOF + DCV during study period treated for 12 weeks. The patients that were treated during 24 weeks were excluded and those treated with peg-interferon. The main endpoint measured was the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary endpoint was SVR at 24 weeks (SVR24).
Results. During the study period, 603 patients were treated in our hospital: 71 with genotype 3. We included 46 patients who were treated with LDV/SOF ± RBV or SOF + DCV for 12 weeks. A 43.75% (7/16) of all patients treated with LDV/SOF achieved SVR12, 90% (9/10) of the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the patients treated with SOF+DCV achieved SVR12. There was statistically significant difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection.
Conclusions.  In conclusion, in our cohort of patients, the combination of SOF + DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those without cirrhosis (SVR12 100% in both combinations). All patients who achieved SVR12 also achieved SVR24, regardless of the regimen received.

Rev Esp Quimioter 2017; 31(1): 35-42 [Full-text PDF]

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Rev Esp Quimioter 2018; 31(1): 13-20

URISCAM project: Multicenter evaluation of the UF-Series cytometer in the urinary tract infections screening

MARÍA DEL MONTE JARABO, MARÍA ÁNGELES ASENCIO, RAFAEL CARRANZA, ÓSCAR HERRÁEZ, MARÍA HUERTAS, ÁNGEL ARIAS-ARIAS, OLGA REDONDO, MARÍA ÁNGELES GALÁN, MARÍA SOLEDAD ILLESCAS, PILAR ZAMARRÓN, SONIA SOLÍS, SILVIA JIMÉNEZ-ALVAREZ

Introduction. Urine culture, the gold standard to confirm the presence of urinary tract infection (UTI), is the most requested assay in the microbiology department. Our objective was to determine the diagnostic yield of the UF-Series cytometer as a screening method for UTI.
Material and methods. All the urine samples sent to the six Microbiology Laboratories participating in a period of 5 working days were analyzed. We collected demographic variables, apart from those variables related to urine samples: source and sample type (midstream, catheterized or nephrostomy urines), collection with/without boric acid, cytometer parameters (leukocyturia, bacteriuria, bacteria morphology and epithelial cells) and urine culture results. ROC curves were plotted to determine predictive capacity of the cytometer.
Results. A sample of 2,468 patients with average age of 53 years were processed (ratio women:men 2:1). Urine culture detected 23% of positive urine samples. The predictor variables of UTI were: morphology of bacilli, bacteriuria ≥21 bacteria/µL, age ≥65 years, samples collected in the emergency service and hospitalization and preserving conditions. With 21 bacteria/µL as a cut-off point, we obtained a sensitivity of 93.3% and 94.5% negative predictive value, then reducing the samples to be cultured by 28.9% with 1.6% false negatives.
Conclusions. We consider that the UF-Series is a valid and accurate tool for the detection of UTI. Therefore, it could be used as screening method in the clinical practice prior to the urine culture, reducing culture requirement by approximately 30%, with a low false negative rate.

Rev Esp Quimioter 2017; 31(1): 13-20 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(1): 27-34

Analysis on the ambulatory usage of antibiotics at general hospitals in Asturias (2006-2015)

MARÍA LUISA SÁNCHEZ-NÚÑEZ, MANUEL JAVIER VALLINA-VICTORERO, MARÍA ROSARIO BACHILLER-LUQUE, JOSÉ MARÍA PINILLA SÁNCHEZ, JOSÉ MARÍA EIROS

Introduction. The Organization for Economic Co-operation and Development (OECD) emphasize, in its report on health policies from 2017 that, Spain is one of the countries with largest consumption of antibiotics, 21.6 DHD (defined daily dose per 1000 inhibitants per day) in 2014 greater than the average 20.5 DHD in their countries, ranking according to the European Center for Disease Prevention and Control (ECDC) in the 11th place out of 30 European countries in 2016. The outpatient prescription of specialized care is analyzed less frequently, due to the greater contribution in consumption and expenditure of primary care.
Material and methods. A descriptive, observational, and retrospective study of the consumption and expenditure of the J01 group derived from outpatient prescription (outpatient and urgent care) of public hospitals in Asturias, in a period of ten years (2006-2015). Consumption data were obtained using the database of prescription billing of the Health Service of the Principality of Asturias, demographic data were provided by the National Institute of Statistics. Consumption was expressed in DHD and antibiotics expenditure in: expenditure per capita and expenditure in euros per defined daily dose.
Results. The average global ambulatory consumption for the period was 23.4 DHD, corresponding 11.5% (2.7 DHD) to the ambulatory specialty care prescription. In terms of expenditure, it accounted for 13.6% of overall outpatient spending on antibiotics.
Conclusions. Outlay and consumption had opposite tendencies, the expenditure control measures did not have or had little impact on consumption, therefore, independent and spe-cific rationalization measures are required in this area.

Rev Esp Quimioter 2017; 31(1): 27-34 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(1): 43-52

Economic and Health impact of influenza vaccination with adjuvant MF59 in population over 64 years in Spain

ALBERTO PÉREZ-RUBIO, JOSÉ MARÍA EIROS

Introduction. Influenza is an important health problem due to the mortality it can cause directly or indirectly as well as the complications and the economic and social costs it produces. Influenza epidemics are being addressed through vaccination campaigns aimed at preventing cases and complications, and the vaccine is officially recommended, as in the case of Spain, for certain risk groups, such as older people, chronic diseases and institutionalized population. The adjuvanted influenza vaccine with MF59, indicated for population over 65 years, has been shown to be more immunogenic than conventional influenza vaccines. The objective of this study is to assess the impact on the national and regional budget of the seasonal vaccination campaigns carried out in Spain using the MF59 adjuvanted vaccine compared to a conventional vaccine in a population older than 65 years.
Material and methods. We analyzed the budgetary impact of the use of the MF59-adjuvanted vaccine in the national territory and by Autonomous Communities through a modeling of two alternatives, conventional vaccination versus adjuvant vaccination with MF59 in a population older than 65 years. The cases of avoided influenza, avoided complications and avoided costs, as well as the economic impact of the vaccination program have been calculated.
Results. With the available information, the budgetary impact of using the influenza vaccine with MF59 in all the over 65 years, amounts to 6,967,288.10 €, avoiding for the national set a cost of 89.5 million Euros, which represents a potential savings of 82 million Euros and a cost-benefit ratio of 12.83.
Conclusion. The use of the influenza vaccine with the MF59 adjuvant to all those over 65 years would mean an increase in the efficiency of the vaccination programs currently proposed in all the Autonomous Communities and in the Spanish state.

Rev Esp Quimioter 2017; 31(1): 43-52 [Texto completo PDF]

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