Conventional microbiological diagnosis and epidemiology of bacteraemia in a tertiary and a district hospital over a six-year period

269 p.La sepsis es un síndrome clínico de extrema gravedad, con una tasa de mortalidad elevada, una incidencia creciente e importantes costes asociados. Las tasas de morbimortalidad están relacionadas con el retraso en la administración del primer antimicrobiano apropiado. Puesto que el tratamiento empírico se basa en la epidemiología local, es fundamental el seguimiento continuo de las tendencias temporales en la tasa de incidencia, la distribución de especies y los perfiles de sensibilidad a antimicrobianos clave. Además, es importante garantizar que las infecciones del torrente sanguíneo se diagnostican correctamente y que los microorganismos causales, sus sensibilidades y las posibles fuentes primarias de infección se evalúan minuciosamente para permitir una terapia antimicrobiana dirigida óptima. Este trabajo se centra en el estudio del diagnóstico microbiológico de bacteriemia y fungemia por cultivo, analizando la epidemiología, etiología y perfiles de resistencia de los principales microorganismos responsables de infección del torrente sanguíneo a antibióticos clave aislados en el Laboratorio centralizado de Microbiología del Hospital Universitario de Araba durante un período de seis años (2015-2020), evaluando dos ensayos rápidos de antibiograma directo, e investigando el papel potencial del tiempo de positivización en el diagnóstico de bacteriemia. Así mismo, se evalúa el impacto de la pandemia por SARS-CoV-2 en la utilización de hemocultivos y se describen las características de la bacteriemia en pacientes infectados con SARS-CoV-2

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.This research was funded by the University of the Basque Country UPV/EHU (GIU17/032)

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.This research was funded by the University of the Basque Country UPV/EHU (GIU20/048; PA20/03), Spain

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective