Does selective digestive decontamination (SDD) increase antibiotic resistance? Long-term comparison of two intensive care units (with and without SDD) of the same tertiary hospital.

PURPOSE: The aim of this study was to to compare the antimicrobial resistance rate and its relationship with the antibiotic consumption in two separate Intensive Care Units (ICUs) of the same hospital, one with and other without selective decontamination of the digestive tract (SDD). METHODS: We performed a retrospective study in the two ICUs of the Araba University Hospital. Trauma and neurosurgical patients are admitted to the SDD-ICU, and general digestive surgery patients go to the no SDD-ICU. From 2014 to 2018 we analyzed the number of isolates, and the bacterial resistance trends of 47 antimicrobial-microorganism combinations. Additionally, antimicrobial consumption was estimated in both ICUs. Resistance rates were also compared with those reported in ENVIN-HELICS Spanish national registry. RESULTS: In the ICU with SDD protocol, there was a significant decrease in the resistance of E. coli to amoxicillin/clavulanic acid and in the resistance of E. faecalis to high concentration of gentamycin and high concentration of streptomycin. A significant increase of resistance of Staphylococcus coagulasa negative (CoNS) to linezolid in the no SDD-ICU was also detected. Overall, the level of resistance in the SDD-ICU was lower or of the same order than in the ICU without SDD and that reported in the Spanish national registry. CONCLUSIONS: SDD had neither a clinically relevant impact on emergence and spread of resistance, nor in the overall systemic antimicrobial use. The patient type rather than the SDD protocol showed to condition the ecology and therefore, the resistance rate in the ICUs.

Ceftaroline and Avibactam Removal by Continuous Renal Replacement Therapies: An in vitro Study.

INTRODUCTION: Continuous renal replacement therapies (CRRTs) are frequently used in critically ill patients; however, there are scarce in vitro and in vivo studies showing the extracorporeal elimination of ceftaroline and avibactam. The aim of this study was to assess, through an in vitro model, the extracorporeal elimination of ceftaroline and avibactam by continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodiafiltration (CVVHDF), and continuous veno-venous hemodialysis (CVVHD), using a polysulfone hemofilter. METHODS: Simulated in vitro experiments were performed using a multiFiltrate machine with a 1.4 m2 Ultraflux® AV600S polysulfone hemofilter. Isofundin® without or with bovine serum albumin was circulated as vehicle for ceftaroline or avibactam. Pre-filter, post-filter, and effluent samples were taken over a period of 60 min, and they were immediately stored at 4°C until processed in the same day. The quantification of ceftaroline and avibactam in the samples was performed by high-performance liquid chromatography with ultraviolet detection. Protein binding, extraction coefficient (EC), and extracorporeal clearance (CLCRRT) were calculated. RESULTS: The elimination of both ceftaroline and avibactam during the three extracorporeal modalities followed first-order pharmacokinetics. Regardless of the CRRT technique, EC values for both molecules were around 1, similar to the unbound fraction of avibactam (0.96) and higher than the unbound fraction of ceftaroline (0.79). CLCRRT of ceftaroline ranged from 15.63 to 17.66 mL/min when CVVH and CVVHD were used with a flow rate of 1,000 mL/h, and from 29.25 to 32.95 mL/min for the CVVHDF modality with a flow rate of 2,000 mL/h. For avibactam, CLCRRT ranged from 15.07 to 18.82 mL/min for CVVH and CVVHD, and from 33.74 to 34.13 mL/min for CVVHDF. DISCUSSION: Avibactam and ceftaroline are extensively removed through the polysulfone membrane, and a dose adjustment may be recommended for patients under CRRT to ensure pharmacodynamic target achievement.

[Antimicrobial susceptibility cumulative reports]. / Informes acumulados de sensibilidad a los antimicrobianos.

Cumulative reports on antimicrobial susceptibility tests data are important for selecting empirical treatments, as an educational tool in programs on antimicrobial use, and for establishing breakpoints defining clinical categories. These reports should be based on data validated by clinical microbiologists using diagnostic samples (not surveillance samples). In order to avoid a bias derived from including several isolates obtained from the same patient, it is recommended that, for a defined period, only the first isolate is counted. A minimal number of isolates per species should be presented: a figure of >=30 isolates is statistically acceptable. The report is usually presented in a table format where, for each cell, information on clinically relevant microorganisms-antimicrobial agents is presented. Depending on particular needs, multiple tables showing data related to patients, samples, services or special pathogens can be prepared.

[Pharmacokinetic/pharmacodynamic analysis in microbiology: a tool for the evaluation of the antimicrobial treatment]. / Análisis farmacocinético-farmacodinámico en microbiología: herramienta para evaluar el tratamiento antimicrobiano.

The selection of multiresistant microorganisms, as a side-effect of the use of antimicrobials, together with the lack of new therapeutic drugs expected in the near future, forces to a rational use of antibiotics. The optimisation of antibacterial treatments based on pharmacokinetic/pharmacodynamic analysis (PK/PD) may contribute to prolong the life of antibiotics and to contain the bacterial resistance to them. A review is made of the importance of the appropriateness of the dose regimen selected, the application of PK/PD analysis of antimicrobials, the Monte Carlo simulation, PK/PD indices for efficacy, and PK/PD cut-off points. PK/PD analysis is also applicable to the prevention of bacterial resistance. Different methods have been used to study the factors that lead to its emergence and spread, such as in vitro and animal models, and resistance prevention studies (mutant selection window). Although the PK/PD analysis is a very useful tool for the selection of the most appropriate dose regimen of antibiotics, several problems limit its use in clinical practice.

Optimizing Antibiotic Therapy for Stenotrophomonas maltophilia Infections in Critically Ill Patients: A Pharmacokinetic/Pharmacodynamic Approach.

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected.

Spanish Antibiogram Committee (COESANT) recommendations for cumulative antibiogram reports.

The Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) presents in this document a series of recommendations intending to unify how cumulative antibiogram reports must be made in Clinical Microbiology Spanish laboratories. This article is based on the information included in the Clinical Microbiology Procedure No. 51, «Preparation of cumulative reports on antimicrobial susceptibility¼ of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), published in 2014. The recommendations also include the modifications in the definition of clinical interpretive categories recently published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2019. Its final objective is to establish a homogeneous way of preparing these summaries to compare results from different centers or aggregate the information from these in order to carry out an adequate local or even national surveillance regarding the evolution of antimicrobial susceptibility.

Pharmacokinetic/Pharmacodynamic Analysis of Tedizolid Phosphate Compared to Linezolid for the Treatment of Infections Caused by Gram-Positive Bacteria.

Tedizolid and linezolid have antibacterial activity against the most important acute bacterial skin and skin-structure infection (ABSSSIs) pathogens. The objective of this work was to apply PK/PD analysis to evaluate the probability of attaining the pharmacodynamic target of these antimicrobials based on the susceptibility patterns of different clinical isolates causing ABSSSI. Pharmacokinetic and microbiological data were obtained from the literature. PK/PD breakpoints, the probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated by Monte Carlo simulation. PTA and CFR are indicative of treatment success. PK/PD breakpoints of tedizolid and linezolid were 0.5 and 1 mg/L, respectively. Probability of treatment success of tedizolid was very high (>90%) for most staphylococci strains, including MRSA and coagulase-negative staphylococci (CoNS). Only for methicillin- and linezolid-resistant S. aureus (MLRSA) and linezolid resistant (LR) CoNS strains was the CFR of tedizolid very low. Except for LR, daptomycin-non-susceptible (DNS), and vancomycin-resistant (VRE) E. faecium isolates, tedizolid also provided a high probability of treatment success for enterococci. The probability of treatment success of both antimicrobials for streptococci was always higher than 90%. In conclusion, for empiric treatment, PK/PD analysis has shown that tedizolid would be adequate for most staphylococci, enterococci, and streptococci, even those LR whose linezolid resistance is mediated by the cfr gene.

Evaluation of the adequacy of the antimicrobial therapy of invasive Haemophilus influenzae infections: A pharmacokinetic/pharmacodynamic perspective.

INTRODUCTION: In Europe, non-typeable H. influenzae (NTHi) is the leading cause of invasive H. influenzae disease in adults and is associated with high mortality. The goal of this study was to determine whether current antimicrobial treatments for H. influenzae infection in Spain are suitable based on their probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) targets. METHODS: Pharmacokinetic parameters for the antibiotics studied (amoxicillin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, ceftriaxone, imipenem and ciprofloxacin) and susceptibility data for H. influenzae were obtained from literature. A Monte Carlo simulation was used to estimate the probability of target attainment (PTA), defined as the probability that at least a specific value of a PK/PD index is achieved at a certain MIC, and the cumulative fraction of response (CFR), defined as the expected population PTA for a specific drug dose and a specific microorganism population. RESULTS: Regardless of dosing regimen, all antibiotics yielded CFR values of 100% or nearly 100% for all strains, including BL+, BL- and BLNAR, except amoxicillin and ampicillin for BL+. Thus, if an infection is caused by BL+ strains, treatment with amoxicillin and ampicillin has a high probability of failure (CFR≤8%). For standard doses of amoxicillin, amoxicillin/clavulanic acid and imipenem, PK/PD breakpoints were consistent with EUCAST clinical breakpoints. For the other antimicrobials, PK/PD breakpoints were higher than EUCAST clinical breakpoints. CONCLUSIONS: Our study confirms by PK/PD analysis that, with the antimicrobials used as empirical treatment of invasive H. influenzae disease, a high probability of therapeutic success can be expected.

Quantification of Ceftaroline in Human Plasma Using High-Performance Liquid Chromatography with Ultraviolet Detection: Application to Pharmacokinetic Studies.

This study was conducted to develop a rapid, simple and reproducible method for the quantification of ceftaroline in plasma samples by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Sample processing consisted of methanol precipitation and then, after centrifugation, the supernatant was injected into the HPLC system, working in isocratic mode. Ceftaroline was detected at 238 nm at a short acquisition time (less than 5 min). The calibration curve was linear over the concentration range from 0.25 to 40 µg/mL, and the method appeared to be selective, precise and accurate. Ceftaroline in plasma samples was stable at -80 °C for at least 3 months. The method was successfully applied to characterize the pharmacokinetic profile of ceftaroline in two critically ill patients and to evaluate whether the pharmacokinetic/pharmacodynamic (PK/PD) target was reached or not with the dose regimen administered.

Identification of a New HIV-1 BC Intersubtype Circulating Recombinant Form (CRF108_BC) in Spain.

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.

The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant.

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.

Executive summary of the Consensus Document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and of the Spanish Association of Surgeons (AEC) in antibiotic prophylaxis in surgery.

Antibiotic prophylaxis in surgery is one of the most effective measures for preventing surgical site infection, although its use is frequently inadequate and may even increase the risk of infection, toxicities and bacterial resistance. As a result of advances in surgical techniques and the emergence of multidrug-resistant organisms, the current guidelines for prophylaxis need to be revised. La Sociedad Española de Enfermedades Infecciosas (Spanish Society of Infectious Diseases and Clinical Microbiology) (SEIMC) together with the Asociación Española de Cirujanos (Spanish Association of Surgeons) (AEC) have revised and updated the recommendations for antibiotic prophylaxis to adapt them to any type of surgical intervention and to current epidemiology. This document gathers together the recommendations on antimicrobial prophylaxis in the various procedures, with doses, duration, prophylaxis in special patient groups, and in epidemiological settings of multidrug resistance to facilitate standardized management and the safe, effective and rational use of antibiotics in elective surgery.

Executive summary of the Consensus Document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and of the Spanish Association of Surgeons (AEC) in antibiotic prophylaxis in surgery. / Resumen ejecutivo del Documento de Consenso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y de la Asociación Española de Cirujanos (AEC) en profilaxis antibiótica en cirugía.

Antibiotic prophylaxis in surgery is one of the most effective measures for preventing surgical site infection, although its use is frequently inadequate and may even increase the risk of infection, toxicities and antimicrobial resistance. As a result of advances in surgical techniques and the emergence of multidrug-resistant organisms, the current guidelines for prophylaxis need to be revised. The Sociedad Española de Enfermedades Infecciosas (Spanish Society of Infectious Diseases and Clinical Microbiology) (SEIMC) together with the Asociación Española de Cirujanos (Spanish Association of Surgeons) (AEC) have revised and updated the recommendations for antibiotic prophylaxis in surgery to adapt them to any type of surgical intervention and to current epidemiology. This document gathers together the recommendations on antimicrobial prophylaxis in the various procedures, with doses, duration, prophylaxis in special patient groups, and in epidemiological settings of multidrug resistance to facilitate standardized management and the safe, effective and rational use of antibiotics in elective surgery.

Are oral cefuroxime axetil, cefixime and cefditoren pivoxil adequate to treat uncomplicated acute pyelonephritis after switching from intravenous therapy? A pharmacokinetic/pharmacodynamic perspective.

OBJECTIVES: The goal of this study is to assess, by means of pharmacokinetic/pharmacodynamic (PK/PD) analysis using the Monte Carlo simulation, the adequacy of oral cephalosporins cefuroxime axetil, cefixime and cefditoren at different dosing regimens as switch therapy after intravenous cephalosporin treatment in uncomplicated acute pyelonephritis. METHODS: The methodology included: (i) dosing regimen selection and acquisition of pharmacokinetic data; (ii) microbiological data acquisition; and (iii) Monte Carlo simulation to estimate the PTA (probability of PK/PD target attainment) and CFR (cumulative fraction of response), as indicators of treatment success. RESULTS: At the current susceptibility breakpoints defined by EUCAST and CLSI for either cefuroxime axetil or cefixime, the probability of bactericidal target attainment is zero for the dosage regimens simulated. Considering the bactericidal target %fT>MIC>70%, the likelihood of the cefuroxime 500-mg q8h regimen or the cefixime 200-mg q12h regimen producing this exposure or achieving this target is only above 90% for organisms yielding MICs≤0.5mg/l and MICs≤0.25mg/l, respectively. Cefditoren pivoxil 400mg q12h provided probabilities of bactericidal target attainment of 80% or higher for MICs≤0.03mg/l, and ≤0.25mg/l if considering total instead of free drug concentrations. CONCLUSIONS: The results of the PK/PD target attainment analysis reveal that the likelihood of treatment success based upon the current breakpoints proposed by either EUCAST or CLSI is low. Of the three cephalosporins, cefixime 400mg q12h prove to be the best option in oral APN treatment, although this regimen is currently off label.

Endophthalmitis caused by Fusarium: An emerging problem in patients with corneal trauma. A case series.

BACKGROUND: Although fortunately very rare in countries with a temperate climate, certain factors, such as clinical or pharmacological immunosuppression, may cause Fusarium-related fungal infections to become an emerging problem. Moreover, Fusarium is one of the most important etiological agents in exogenous endophthalmitis, which is often favored by the disruption of the epithelial barriers. AIMS: The aim of this series of clinical cases is to identify characteristic clinical findings that may allow an early diagnosis and more efficient management of this ophthalmologic emergency. METHODS: Three cases of endophthalmitis due to Fusarium solani and Fusarium oxysporum, diagnosed in 2009, 2010, and 2014 in patients from two different health regions belonging to the same health system and separated by around 43 miles, are presented. The Fusarium isolates were initially identified microscopically and the species subsequently confirmed by sequencing the elongation factor alpha (EFα) and internal transcribed spacers (ITS). Susceptibility to antifungal agents was determined using the EUCAST broth dilution method. RESULTS: Evolution was poor as two of the three patients progressed to phthisis bulbi despite surgical measures and broad-spectrum antifungal antibiotic therapy. CONCLUSIONS: It is essential to rapidly instigate multidisciplinary measures to combat suspected endophthalmitis due to Fusarium given the poor prognosis of this type of infection.

[Acute complicated and uncomplicated pyelonephritis in the emergency department: process-of-care indicators and outcomes]. / Pielonefritis aguda complicada y no complicada en urgencias: indicadores de proceso y resultado.

OBJECTIVES: To assess process-of-care indicators and outcomes in acute pyelonephritis (APN) in a general hospital emergency department, and compare them between uncomplicaed and complicated APN. MATERIAL AND METHODS: Retrospective study of consecutive patients discharged with a diagnosis of APN. We studied health processof- care indicators (percentage admitted, avoidable hospitalization, appropriate initial antibiotic therapy, urine and blood cultures) and outcomes (hospital length of stay [LOS], discharge from the emergency department, revisits, mortality, yields of microbiological tests ordered). RESULTS: A total of 529 cases (59% of them complicated) were included. Patients with uncomplicated APN were significantly younger on average (mean, 39 years) than patients with complicated APN (56 years). Escherichia coli was the most common pathogen identified, although the percentage of E coli infection was lower in patients with complicated APN (78%) than in patients with uncomplicated APN (95%). The rates of admission and orders for urine and blood cultures were significantly higher and hospital LOS was longer in the group with complicated APN. Moreover, these patients had even longer stays if the initial antibiotic therapy was inappropriate. Significantly more patients with uncomplicated APN were discharged from the emergency department. Sixty-one percent of patients with uncomplicated APN were admitted; 9% of these cases were considered avoidable hospitalizations. CONCLUSION: Complicated APN is diagnosed more often in older patients, and E coli infection causes a smaller proportion of these cases. Hospital LOS is longer in complicated APN and more urine and blood cultures are ordered. Patients with uncomplicated APN are more often discharged from the emergency department, although the number of avoidable hospitalizations seems high based on the rate found in this study.

OBJETIVO: Evaluar distintos indicadores de proceso y de resultado en la pielonefritis aguda (PNA) en el servicio de urgencias (SU) de un hospital general y compararlos entre las PNA no complicadas (PNAnc) y las complicadas (PNAc). METODO: Estudio retrospectivo de pacientes consecutivos con diagnóstico al alta de PNA. Se estudiaron indicadores de proceso (porcentaje de ingresos, hospitalización evitable, adecuación de antibioterapia inicial, urocultivos y hemocultivos obtenidos) y de resultado (duración ingreso, altas desde urgencias, reingresos, mortalidad, rendimiento pruebas microbiológicas). RESULTADOS: Se incluyeron 529 pacientes, el 59% con PNAc. La edad media de los pacientes con PNAnc fue significativamente inferior a la de los pacientes con PNAc (39 frente a 56 años). Escherichia coli fue el microorganismo más frecuente, aunque en el grupo de PNAc el porcentaje de aislados de E. coli fue menor (78% frente a 95%). En el grupo de PNAc los ingresos, los urocultivos y hemocultivos obtenidos, y la estancia fueron significativamente mayores y, además, esta última fue aún mayor si la antibioterapia inicial fue inadecuada. El porcentaje de altas desde el SU fue significativamente mayor en las PNAnc. El 61% de las mujeres con PNAnc fueron ingresadas y, en el 9% de estos casos, las hospitalizaciones se consideraron evitables. CONCLUSIONES: Las PNAc se diagnosticaron en personas de más edad, en las que la etiología por E. coli fue menor, y la estancia hospitalaria y la solicitud de urocultivos y hemocultivos fueron mayores. Las altas desde el SU fueron más frecuentes en PNAnc, aunque el porcentaje de ingresos convencionales, a juzgar por las hospitalizaciones que fueron consideradas evitables, fue elevado.

Trends in antimicrobial utilization at a Spanish general hospital during a 5-year period.

PURPOSE: Antimicrobials are a major part of hospital pharmacy budgets and must be considered in resource planning and spending projections. This study describes the profile of antibiotic use at a medium-sized hospital (by examining the ICU separately) and analyses its evolution over the period 1996-2000. METHODS: Descriptive and retrospective study. Pharmacy records were reviewed to identify oral and parenteral antimicrobial agents administered to inpatients. Results were expressed in Daily Defined Doses (DDD) per 100 stays and day. RESULTS: During the 5-year study period 176.162 DDD/100 s-d of antibiotics were consumed in the ICU, whereas in the rest of the hospital usage was much lower (54.438 DDD/100 s-d). Aminoglycosides, cephalosporins, penicillins, glycopeptides and carbapenems were the most commonly used groups of antimicrobials in the ICU, and penicillins, cephalosporins, trimethoprim/sulfonamide combinations, aminoglycosides and quinolones in the rest of the hospital. CONCLUSIONS: ICUs have some special features which make them different to the other inpatient areas. Because of that fact we consider it important to study this specific patient-care area separately.