Virulence genotype and phenotype of two clinical isolates of Arcobacter butzleri obtained from patients with different pathologies.

The surge in human arcobacteriosis has increased interest in determining the mechanisms involved in the pathogenesis of Arcobacter butzleri. Here, genomic analyses and in vitro Caco-2 infection, motility, urease and antimicrobial susceptibility testing (AST) assays were used to characterise the virulence and antimicrobial resistance (AMR) determinants of strains HC-1, isolated from a patient with travellers' diarrhoea, and HC-2, isolated from another with pruritus. AMR determinants conferring resistance to tetracycline (tetO, present in both genomes) and to ampicillin and amoxicillin-clavulanic acid (bla3, present in HC-2) were identified. The same determinants associated with flagellum, chemotaxis, adhesion and invasion were detected in both, but HC-1 lacked eight flagellar genes. The urease cluster was only present in HC-1. Motility and urease tests confirmed the genetic differences between strains, but no genetic marker related to the inability of HC-2 to adhere and invade was identified. This inability could be conditioning the patient's pathology.

Validation of an expanded, in-house library and an optimized preparation method for the identification of fungal isolates using MALDI-TOF mass spectrometry.

The goal of this study was to validate an optimized sample preparation method for filamentous fungal isolates coupled with the use of an in-house library for the identification of moulds using Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) in a multicenter context. For that purpose, three Spanish microbiology laboratories participated in the identification of 97 fungal isolates using MALDI-TOF MS coupled with the Filamentous Fungi library 3.0 (Bruker Daltonics) and an in-house library containing 314 unique fungal references. The isolates analyzed belonged to 25 species from the genus Aspergillus, Fusarium, Scedosporium/Lomentospora, the Mucorales order and the Dermatophytes group. MALDI-TOF MS identification was carried out from hyphae resuspended in water and ethanol. After a high-speed centrifugation step, the supernatant was discarded and the pellet submitted to a standard protein extraction step. The protein extract was analyzed with the MBT Smart MALDI Biotyper system (Bruker Daltonics). The rate of accurate, species-level identification obtained ranged between 84.5% and 94.8% and the score values were 1.8 for 72.2-94.9% of the cases. Two laboratories failed to identify only one isolate of Syncephalastrum sp. and Trichophyton rubrum, respectively and three isolates could not be identified in the third center (F. proliferatum, n = 1; T.interdigitale, n = 2). In conclusion, the availability of an effective sample preparation method and an extended database allowed high rates of correct identification of fungal species using MALDI-TOF MS. Some species, such as Trichophyton spp. are still difficult to identify. Although further improvements are still required, the developed methodology allowed the reliable identification of most fungal species.

MALDI-TOF mass spectrometry has been improved as a diagnostic method for the rapid and reliable identification of filamentous fungi by means of the creation of an expanded database containing reference protein spectra of the most clinically impacting fungal species.

Haemophilus influenzae Type a Sequence Type 23, Northern Spain.

Two consecutive cases of Haemophilus influenzae type a sequence type 23 invasive infection in 2 children attending the same daycare in 2019 triggered epidemiologic surveillance of H. influenzae infections in northern Spain. Despite the invasiveness potential of this virus strain, we detected no additional cases for 2013-2020.

Pharmacokinetic/pharmacodynamic evaluation of the antimicrobial therapy of pneumococcal invasive disease in adults in post-PCV13 vaccine period in Madrid, Spain.

The objective of our study was to evaluate by pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the antimicrobials used for the treatment of invasive pneumococcal disease (IPD) in adults, including meningitis, are adequate considering the susceptibility profile of S. pneumoniae in Spain after the implantation of PVC13 vaccine. Pharmacokinetic parameters of benzylpenicillin and cefotaxime were obtained from the literature, and susceptibility data of invasive S. pneumoniae strains recovered in 2017 (post-PCV13 vaccination period) were provided by the Public Health Regional Laboratory of Madrid. We have also studied levofloxacin because it is used to treat pneumococcal pneumonia previously to be diagnosed as bacteremic pneumonia. Monte Carlo simulation was used to estimate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). All doses of benzylpenicillin except 2 mU q6h provide a high probability of treatment success for MIC values ≤ 1 mg/L; 4 mU q4h is even useful for MIC values up to 4 mg/L. This high dose, used for the treatment of meningitis, also provides high probability of treatment success for MIC ≤ 0.5 mg/L. At the susceptibility EUCAST breakpoint (≤ 0.5 mg/L), cefotaxime provides a high rate of PD target achievement, even at the lowest dose (1 g q8h). For meningitis, 2 g q6h ensures probabilities of target attainment ≥90% for MIC up to 1 mg/L. Our study confirms that after the implementation of PCV13 vaccine, the treatment with benzylpenicillin and cefotaxime provides high probability of the therapy success of IPD, including meningitis.

Antibiotic susceptibility trend before and after long-term use of selective digestive decontamination: a 16 year ecological study.

OBJECTIVES: The aim of this study was to compare antimicrobial susceptibility rates in a Spanish ICU before and after the introduction of selective digestive decontamination (SDD) and also to compare these with susceptibility data from other Spanish ICUs without SDD. METHODS: We performed a retrospective study in the ICU of the University Hospital of Alava, where SDD was implemented in 2002. The SDD protocol consisted of a 2% mixture of gentamicin, colistin and amphotericin B applied on the buccal mucosa and a suspension of the same drugs in the gastrointestinal tract; additionally, for the first 3 days, systemic ceftriaxone was administered. From 1998 to 2013 we analysed the susceptibility rates for 48 antimicrobial/organism combinations. Interrupted time series using a linear dynamic model with SDD as an intervention was used. Data from other ICUs were obtained from the ENVIN-HELICS national registry. RESULTS: Only amoxicillin/clavulanic acid against Escherichia coli and Proteus mirabilis, and a high concentration of gentamicin against Enterococcus faecalis, resulted in a significant decrease in the susceptibility rate after the implementation of SDD, with a drop of 20%, 27% and 32%, respectively. Compared with other Spanish ICUs without SDD, the susceptibility rate was higher in the ICU of our hospital in most cases. When it was lower, differences were <10%, except for a high concentration of streptomycin against Enterococcus faecium, for which the difference was 19%. CONCLUSIONS: No relevant changes in the overall susceptibility rate after the implementation of SDD were detected. Susceptibility rates were not lower than those in the Spanish ICUs without SDD.

Executive summary of the diagnosis and treatment of urinary tract infection: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC).

Most urinary tract infections (UTI) are uncomplicated infections occurring in young women. An extensive evaluation is not required in the majority of cases, and they can be safely managed as outpatients with oral antibiotics. Escherichia coli is by far the most common uropathogen, accounting for >80% of all cases. Other major clinical problems associated with UTI include asymptomatic bacteriuria, and patients with complicated UTI. Complicated UTIs are a heterogeneous group associated with conditions that increase the risk of acquiring infection or treatment failure. Distinguishing between complicated and uncomplicated UTI is important, as it influences the initial evaluation, choice, and duration of antimicrobial therapy. Diagnosis is especially challenging in the elderly and in patients with in-dwelling catheters. The increasing prevalence of resistant uropathogens, including extended-spectrum ß-lactamases and carbapenemase-producing Enterobacteriaceae, and other multidrug-resistant Gram-negative organisms further compromises treatment of both complicated and uncomplicated UTIs. The aim of these Clinical Guidelines is to provide a set of recommendations for improving the diagnosis and treatment of UTI.

[Ceftaroline breakpoints]. / Puntos de corte de ceftarolina.

Ceftaroline is a new cephalosporin for parenteral use. Notable among its microbiological properties is its ability to inhibit penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus and its good in vitro activity against several microorganisms of clinical interest. The European Committee of Antimicrobial Susceptibility Testing (EUCAST) has defined both epidemiological breakpoints (defining wild-type populations that lack known acquired mechanisms of resistance) and clinical breakpoints for this compound. The Clinical and Laboratory Standards Institute (CLSI) has also defined clinical breakpoints. Based on the microbiological activity of ceftaroline, clinical categories have been defined for enterobacteria, S. aureus, Haemophilus influenzae, Streptococcus pneumoniae, and beta-hemolytic Streptococcus. EUCAST has also established breakpoints based on pharmacokinetic-pharmacodynamic criteria.

Breakpoints for carbapenemase-producing Enterobacteriaceae: is the problem solved?

The imipenem and meropenem breakpoints for Enterobacteriaceae established by the Clinical and Laboratory Standards Institute (CLSI) are somewhat lower than those established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), but are identical for ertapenem and doripenem. The differences are primarily due to the various pharmacokinetic/pharmacodynamic (PK/PD) approaches used to define these breakpoints. Both approaches use the Monte Carlo simulation with a probability of target attainment (PTA) for reaching the PD target of free drug concentration above the minimum inhibitory concentration (MIC) at least 40% of the time (~40%fT >MIC). EUCAST uses PTA mean values with confidence intervals (CIs) of 95% and 99%, whereas the CI used by CLSI is 90%. In addition, CLSI uses an "inflated variance" that takes into account the variability of PK parameters in various types of patients, particularly those who are critically ill. By employing this approach, the susceptible CLSI breakpoint captures a higher number of carbapenemase-producing Enterobacteriaceae (CPE) than EUCAST. EUCAST, however, has recently defined cut-off values for screening CPE. Both committees recommend reporting carbapenem susceptibility results "as tested," demonstrating carbapenemase production only for epidemiological purposes and infection control. New clinical data could potentially modify this recommendation because carbapenemase production also influences specific treatment guidance concerning carbapenems in combination with other antimicrobials in infections due to CPE. This advice should not be followed when imipenem or meropenem MICs are >8mg/L, which is coincident with the EUCAST resistant breakpoints for these carbapenems.

Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG). METHODS: We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than -10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis. FINDINGS: Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference -29·6, 95% CI -50·5 to -8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up. INTERPRETATION: The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis. FUNDING: European Research Council and Fondo de Investigaciones Sanitarias.

[The routine use of the Pneumonia Severity Index in the emergency department: effect on process-of-care indicators and results in community acquired pneumonia]. / Uso rutinario del Pneumonia Severity Index en el servicio de urgencias: efecto sobre los indicadores de proceso y resultado en neumonía adquirida en la comunidad.

OBJECTIVE: To evaluate process-of-care indicators (inappropriate hospitalisation, suitability and early antibiotic treatment) and outcome indicators (length of hospital stay, hospital readmission, ICU admission, and mortality) in the management of community-acquired pneumonia (CAP) when the SEPAR/IDSA guidelines were applied. PATIENTS AND METHODS: An observational retrospective study conducted on patients diagnosed with CAP during the first semester of 2007 and 2008 (186 and 161 patients, respectively) in the emergency unit of a general hospital. Differences in the process-of-care and outcome indicators between 2007 and 2008 (with and without the Pneumonia Severity Index [PSI]) were evaluated. Moreover, the indicators were compared with those obtained in 2006 (110 patients), when the current guidelines were those of SEQ/ATS. RESULTS: The SEPAR/IDSA guidelines improved the following process-of-care indicators: appropriateness of treatment, unjustified hospital readmission (39.4% in 2006 vs. 8.5% in 2007 [P<.001], and 17,2% in 2008 [P=.005]), and early treatment. However, outcome indicators did not change. In 2008, a decrease in the mortality of the patients of risk classes IV-V in which the PSI had been estimated was observed in comparison with the patients in which the PSI was not estimated (2.3% vs. 28.3%; P<.001). Moreover, the mortality rate of the patients of risk classes IV-V in which the PSI had been estimated was lower than those measured using the SEQ/ATS guidelines (22.7%; P=.003). CONCLUSION: SEPAR/IDSA guidelines decreased the unjustified hospital readmission. In the second year of its application an increase in the number of patients who received early treatment, and a decrease of the mortality rate of the patients of risk classes IV-V in which the PSI had been estimated, were also observed.

Pharmacokinetic/Pharmacodynamic Analysis of Oral Calcium Fosfomycin: Are Urine Levels Sufficient to Ensure Efficacy for Urinary Tract Infections?

Urinary tract infections (UTIs) are extremely common and a major driver for the use of antimicrobials. Calcium fosfomycin is an old antibiotic indicated for the treatment of UTIs; however, data about its urine pharmacokinetic profile are scarce. In this work, we have evaluated the pharmacokinetics of fosfomycin from urine concentrations after oral administration of calcium fosfomycin to healthy women. Moreover, we have assessed, by pharmacokinetic/pharmacodynamic (PK/PD) analysis and Monte Carlo simulations, its effectiveness considering the susceptibility profile of Escherichia coli, the main pathogen involved in UTIs. The accumulated fraction of fosfomycin excreted in urine was around 18%, consistent with its low oral bioavailability and its almost exclusively renal clearance by glomerular filtration as unchanged drug. PK/PD breakpoints resulted to be 8, 16, and 32 mg/L for a single dose of 500 mg, a single dose of 1000 mg, and 1000 mg q8h for 3 days, respectively. For empiric treatment, the estimated probability of treatment success was very high (>95%) with the three dose regimens, considering the susceptibility profile of E. coli reported by EUCAST. Our results show that oral calcium fosfomycin at a dose level of 1000 mg every 8 h provides urine concentrations sufficient to ensure efficacy for the treatment of UTIs in women.

Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study.

BACKGROUND: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria. METHODS: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment. FINDINGS: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance. INTERPRETATION: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy. FUNDING: European Research Council.

Population pharmacokinetics of prophylactic cefoxitin in patients undergoing colorectal surgery.

PURPOSE: To elucidate whether a dose of 2 g cefoxitin as a prophylactic agent in patients undergoing elective colorectal surgery is able to maintain free drug concentrations above the minimum inhibitory concentration of the microorganisms involved in surgical site infection. METHODS: This was a prospective study involving 56 patients electively undergoing rectal or colon surgery. All plasma concentration-time data were analyzed simultaneously using the population approach to estimate population pharmacokinetic parameters and study the influence of the subjects' demographic characteristics, disease status, surgical procedure, and clinical laboratory values on the pharmacokinetic properties of cefoxitin. RESULTS: A one-compartment open model was chosen to describe plasma concentrations of cefoxitin. Since cefoxitin is eliminated almost entirely via the kidney, creatinine clearance was identified as a covariate of cefoxitin clearance. The relationship between total cefoxitin clearance (CL) and creatinine clearance (CL(CR)) was best described using a nonlinear model [CL = 11.5 × (CL(CR)/77)(0.52)]. The population apparent volume of distribution was 12 L. Computer simulations carried out to determine the probability to maintain free plasma concentrations above 8 mg/L (the concentration threshold for susceptible bacteria) 2 h after drug administration revealed that this probability decreased from 84% in patients with a CL(CR) of 40 mL/min to 28% in patients with a CL(CR) of 100 mL/min. CONCLUSIONS: To ensure cefoxitin target concentrations during surgery, we recommend that cefoxitin be administered every 1.5 h in patients with a CL(CR) ≥ 60 mL/min and every hour if the CL(CR) is ≥ 100 mL/min. Administration by continuous infusion preceded by a bolus injection should also be considered.

Human papillomavirus (HPV) genotype distribution in women with abnormal cervical cytology in the Basque Country, Spain.

INTRODUCTION: The aim of this study was to analyze the distribution of human papillomavirus (HPV) genotypes in cytologically abnormal cervical samples from 106 women living in a region of the north of Spain. METHODS: Cytological classification was reported according to the 2001 Bethesda System and HPV genotyping was performed by Roche Linear Array. RESULTS: The overall HPV prevalence was 69.8% with 30 different HPV genotypes detected. The prevalence of HR (high-risk) HPV types and pHR (probable high-risk) HPV types in positive samples was 94.3%, 78.1% and 100% in patients with ASCUS, LSIL and HSIL/CC, respectively, with no significant differences. The most frequent type was the HPV 16, present in 29.7% of all positive samples, followed by HPV 51 (17.5%), HPV 53 and 42 (16%), HPV 52 (12%), HPV 39 (10.8%), HPV 18 and 58 (9.4%) and HPV 66 (8.1%). No significant differences in the percentage of any HPV genotype with the grade of the cytological lesion were detected. The prevalence of HPV co-infection was 58.1% of HPV positive. CONCLUSIONS: This study confirms the high prevalence of high-risk genotypes in women with abnormal cytology living in our geographical area. This information may be useful for the formulation of algorithms for patient management according to the different risks associated with specific high-risk genotypes.

Pharmacokinetic/pharmacodynamic evaluation of amoxicillin, amoxicillin/clavulanate and ceftriaxone in the treatment of paediatric acute otitis media in Spain.

INTRODUCTION: Acute otitis media is the most common respiratory tract infection in infancy and early childhood that is managed with antimicrobial agents. Ninety-three per cent of the cases diagnosed in Spain are treated with antibiotics, and Streptococcus pneumoniae and untypeable Haemophilus influenzae are the most frequently isolated pathogens. The aim of this work was to evaluate the usefulness of amoxicillin, amoxicillin/clavulanate and ceftriaxone for the empirical treatment of acute otitis media, looking at the pharmacokinetic variability and the antimicrobial susceptibility of paediatric strains of the two main pathogens responsible for AOM in Spain, Streptococcus pneumoniae and Haemophilus influenzae. METHODS: Free-drug plasma concentrations were simulated and the probability of target attainment at each minimum inhibitory concentration and the cumulative fraction of response (CFR) were determined. Microbiological susceptibility information was extracted from SAUCE 3 surveillance. RESULTS: CFR with amoxicillin varied from 83% to 96% against S. pneumoniae and from 78% to 86% against H. influenzae. CFR was always >85% with amoxicillin/clavulanate. With the 3-day ceftriaxone regimen, the probability of achieving free concentrations above MIC at 72 hours significantly increased compared to the single dose, with which CFR ranged from 70% to 84%. CONCLUSIONS: High-dose amoxicillin (at least 80 mg/kg/day) should be the first-line therapy in uncomplicated infections, whereas amoxicillin/clavulanate (40 mg/kg/day) should be the choice when additional coverage for H. influenzae is desired. Administration of 3 daily doses of ceftriaxone increases bacteriological eradication probability when compared with one-day regimen, although additional clinical evaluations are necessary to establish the best target attainment with ceftriaxone.

Molecular Epidemiology, Antimicrobial Surveillance, and PK/PD Analysis to Guide the Treatment of Neisseria gonorrhoeae Infections.

The aim of this study was to apply molecular epidemiology, antimicrobial surveillance, and PK/PD analysis to guide the antimicrobial treatment of gonococci infections in a region of the north of Spain. Antibiotic susceptibility testing was performed on all isolates (2017 to 2019, n = 202). A subset of 35 isolates intermediate or resistant to at least two antimicrobials were selected to search for resistance genes and genotyping through WGS. By Monte Carlo simulation, we estimated the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the antimicrobials used to treat gonorrhea, both indicative of the probability of treatment success. In total, 2.0%, 6.4%, 5.4%, and 48.2% of the isolates were resistant to ceftriaxone, cefixime, azithromycin, and ciprofloxacin, respectively. Twenty sequence types were identified. Detected mutations were related to antibiotic resistance. PK/PD analysis showed high probability of treatment success of the cephalosporins. In conclusion, multiple populations of N. gonorrhoeae were identified. We can confirm that ceftriaxone (even at the lowest dose: 250 mg) and oral cefixime are good candidates to treat gonorrhea. For patients allergic to cephalosporins, ciprofloxacin should be only used if the MIC is known and ≤0.125 mg/L; this antimicrobial is not recommended for empirical treatment.

Pseudomonas aeruginosa Susceptibility in Spain: Antimicrobial Activity and Resistance Suppression Evaluation by PK/PD Analysis.

Pseudomonas aeruginosa remains one of the major causes of healthcare-associated infection in Europe; in 2019, 12.5% of invasive isolates of P. aeruginosa in Spain presented combined resistance to ≥3 antimicrobial groups. The Spanish nationwide survey on P. aeruginosa antimicrobial resistance mechanisms and molecular epidemiology was published in 2019. Based on the information from this survey, the objective of this work was to analyze the overall antimicrobial activity of the antipseudomonal antibiotics considering pharmacokinetic/pharmacodynamic (PK/PD) analysis. The role of PK/PD to prevent or minimize resistance emergence was also evaluated. A 10,000-subject Monte Carlo simulation was executed to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) considering the minimum inhibitory concentration (MIC) distribution of bacteria isolated in ICU or medical wards, and distinguishing between sample types (respiratory and non-respiratory). Ceftazidime/avibactam followed by ceftolozane/tazobactam and colistin, categorized as the Reserve by the Access, Watch, Reserve (AWaRe) classification of the World Health Organization, were the most active antimicrobials, with differences depending on the admission service, sample type, and dose regimen. Discrepancies between EUCAST-susceptibility breakpoints for P. aeruginosa and those estimated by PK/PD analysis were detected. Only standard doses of ceftazidime/avibactam and ceftolozane/tazobactam provided drug concentrations associated with resistance suppression.

[Selective decontamination of the digestive tract: repercussions on microbiology laboratory workload and costs, and antibiotic resistance trends]. / Descontaminación digestiva selectiva: repercusión en la carga de trabajo y el coste del laboratorio de microbiología y tendencias en la resistencia bacteriana.

INTRODUCTION: This study determines the workload and cost of implementing selective digestive decontamination in the microbiology laboratory, and reports the impact on microbial flora and bacterial resistance trends in the intensive care unit (ICU). METHODS: The total microbiological workload and cost were quantified, as well as the part charged to the petitioning service, in the year before and the year after introducing the procedure. Changes in microbial flora were evaluated and bacterial resistance trends were analyzed over 12 years in 21 sentinel antimicrobial/microorganism combinations. RESULTS: The workload ascribed to the ICU increased by 10% and cost increased by 1.8% in the period after introduction of the procedure (non-significant differences). The increased workload resulting from epidemiological surveillance cultures was compensated by significant reductions in quantitative endotracheal aspirate cultures, blood cultures, exudate cultures, identification tests with antibiograms, and serologies. The procedure has been associated with a significant decrease in Acinetobacter isolates and a significant increase in Enterococcus. Three significant trends of increased resistance were detected, all of them in Pseudomonas aeruginosa (imipenem, tobramycin, and ciprofloxacin). CONCLUSIONS: In our hospital, implementation of selective digestive decontamination did not cause a significant increase in the workload or costs in the microbiology laboratory. Selective digestive decontamination was associated with a significant decrease in Acinetobacter, an increase in Enterococcus, and higher resistance to imipenem, tobramycin and ciprofloxacin in P. aeruginosa.

From CLSI to EUCAST, a necessary step in Spanish laboratories. / Del CLSI al EUCAST, una transición necesaria en los laboratorios españoles.

The Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) presents in this document a simple "roadmap" or decalogue of recommendations, with a view to facilitating the transition from the Clinical and Laboratory Standards Institute (CLSI) to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) antimicrobial susceptibility testing regulations to the Clinical Microbiology Spanish laboratories that still use the CLSI guidelines. The objectives are to adapt the closer European regulations to the Spanish clinical and epidemiological reality and to fully implement the EUCAST recommendations in all microbiology laboratories in Spain.

Recommendations of the Spanish Antibiogram Committee (COESANT) for selecting antimicrobial agents and concentrations for in vitro susceptibility studies using automated systems.

Automated antimicrobial susceptibility testing devices are widely implemented in clinical microbiology laboratories in Spain, mainly using EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints. In 2007, a group of experts published recommendations for including antimicrobial agents and selecting concentrations in these systems. Under the patronage of the Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) and the Study Group on Mechanisms of Action and Resistance to Antimicrobial Agents (GEMARA) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), and aligned with the Spanish National Plan against Antimicrobial Resistance (PRAN), a group of experts have updated this document. The main modifications from the previous version comprise the inclusion of new antimicrobial agents, adaptation of the ranges of concentrations to cover the EUCAST breakpoints and epidemiological cut-off values (ECOFFs), and the inference of new resistance mechanisms. This proposal should be considered by different manufacturers and users when designing new panels or cards. In addition, recommendations for selective reporting are also included. With this approach, the implementation of EUCAST breakpoints will be easier, increasing the quality of antimicrobial susceptibility testing data and their microbiological interpretation. It will also benefit epidemiological surveillance studies as well as the clinical use of antimicrobials aligned with antimicrobial stewardship programs.