Clinical experience of cefiderocol

Infections by antibiotic-resistant microorganisms could be considered a "stealth pandemic" that we fight daily in most hospitals. Some estimates suggest that today 700,000 deaths per year can be attributed to antimicrobial resistance. By the year 2050, it is estimated that this will increase to ten million deaths per year as a result of infections by multidrug-resistant microorganisms. In this context, the availability of antimicrobial therapy that is effective against these pathogens is essential to be able to "save the lives" of our patients. Cefiderocol, a new cephalosporin with a different mechanism of action, will be an essential treatment in many infections caused by resistant aerobic gram-negative bacteria. Cefiderocol has been used to treat patients with complicated urinary tract infections (cUTI); hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), healthcare-associated pneumonia (HAP); in patients with sepsis and bacteremia, some without an identified primary focus of infection

Bartonella Endocarditis in Spain: Case Reports of 21 Cases

Endocarditis por Bartonella; Endocarditis infecciosaBartonella endocarditis; Infective endocarditisEndocarditis per Bartonella; Endocarditis infecciosaBlood culture negative endocarditis (BCNE) is frequent in infective endocarditis (IE). One of the causes of BCNE is fastidious microorganisms, such as Bartonella spp. The aim of this study was to describe the epidemiologic, clinical characteristics, management and outcomes of patients with Bartonella IE from the “Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES)”cohort. Here we presented 21 cases of Bartonella IE. This represents 0.3% of a total of 5590 cases and 2% of the BCNE from the GAMES cohort. 62% were due to Bartonella henselae and 38% to Bartonella quintana. Cardiac failure was the main presenting form (61.5% in B. hensalae, 87.5% in B. quintana IE) and the aortic valve was affected in 85% of the cases (76% in B. henselae, 100% in B. quintana IE). Typical signs such as fever were recorded in less than 40% of patients. Echocardiography showed vegetations in 92% and 100% of the patients with B. henselae and B. quintana, respectively. Culture was positive only in one patient and the remaining were diagnosed by serology and PCR. PCR was the most useful tool allowing for diagnosis in 16 patients (100% of the studied valves). Serology, at titers recommended by guidelines, only coincided with PCR in 52.4%. Antimicrobial therapy, in different combinations, was used in all cases. Surgery was performed in 76% of the patients. No in-hospital mortality was observed. One-year mortality was 9.4%. This article remarks the importance for investigating the presence of Bartonella infection as causative agent in all BCNE since the diagnosis needs specific microbiological tools and patients could benefit of a specific treatment

Mannose-binding lectin gene variants and infections in patients receiving autologous stem cell transplantation

BACKGROUND: Serious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections. METHODS: Prospective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression. RESULTS: A statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria. CONCLUSIONS: Low-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection

The poor accuracy of D-dimer for the diagnosis of prosthetic joint infection but its potential usefulness in early postoperative infections following revision arthroplasty for aseptic loosening

Background: D-dimer was introduced in 2018 as an alternative biomarker for C-reactive protein (CRP) in the diagnostic of prosthetic joint infection (PJI) criteria of the Musculoskeletal Infection Society. We assessed the accuracy of plasma D-dimer for the diagnosis of early, delayed, and late PJI according to Infectious Diseases Society of America (IDSA) criteria, and whether persistently high levels of D-dimer in cases of aseptic loosening (AL) may be predictive of subsequent implant-related infection. Methods: A prospective study of a consecutive series of 187 revision arthroplasties was performed at a single institution.Septic (n = 39) and aseptic revisions (n = 141) were classified based on IDSA criteria. Preoperative assessment of CRP, erythrocyte sedimentation rate (ESR) and D-dimer was performed. Receiver operating curves were used to determine maximum sensitivity and specificity of the biomarkers. The natural progress of D-dimer for AL cases was followed up either until the date of implant-related infection at any time during the first year or 1 year after revision in patients without failure. Clinical outcomes for those AL cases included infection-related failure that required a new surgery or need for antibiotic suppression. Results: Preoperative D-dimer level was significantly higher in PJI cases than in AL cases (p = 0.000). The optimal threshold of D-dimer for the diagnosis of PJI was 1167 ng/mL. For overall diagnosis of PJI, C-reactive protein (CRP) achieved the highest sensitivity (84.6%), followed by erythrocyte sedimentation rate (ESR) and D-dimer (82% and 71.8%, respectively). Plasma D-dimer sensitivity was lower for all PJI types. When combinations of 2 tests were studied, the combined use of ESR and CRP achieved the best accuracy for all types of PJI (76.9%). 4.25% of AL cases had implant failure due to implant-related infection during the first year after the index revision arthroplasty, only the cases with early failure maintained high D-dimer levels

Mannose-binding lectin promoter polymorphisms and gene variants in pulmonary tuberculosis patients from Cantabria (northern Spain)

Mannose-binding lectin is a central molecule of the innate immune system. Mannose-binding lectin 2 promoter polymorphisms and structural variants have been associated with susceptibility to tuberculosis. However, contradictory results among different populations have been reported, resulting in no convincing evidence of association between mannose-binding lectin 2 and susceptibility to tuberculosis. For this reason, we conducted a study in a well genetically conserved Spanish population in order to shed light on this controversial association. We analysed the six promoter and structural mannose-binding lectin 2 gene variants in 107 patients with pulmonary tuberculosis and 441 healthy controls. Only D variant and HYPD haplotype were significantly more frequents in controls which would indicate that this allele could confer protection against pulmonary tuberculosis, but this difference disappeared after statistical correction. Neither the rest of alleles nor the haplotypes were significantly associated with the disease. These results would indicate that mannose-binding lectin promoter polymorphisms and gene variants would not be associated with an increased risk to pulmonary tuberculosis. Despite the slight trend of the D allele and HYPD haplotype in conferring protection against pulmonary tuberculosis, susceptibility to this disease would probably be due to other genetic factors, at least in our population

Post-traumatic Endophthalmitis Caused by Nocardia nova

Introduction: Nocardia nova complex has been associated with infections in both immunocompetent and immunocompromised patients. Infection can be localized or disseminated, affecting skin and soft tissues, the respiratory system, bones and joints, the circulatory system and especially the central nervous system. Ocular infections such as keratitis, scleritis, conjunctivitis, dacryocystitis, orbital cellulitis and endophthalmitis due to Nocardia spp. are infrequently reported, and usually described after penetrating corneal trauma or ocular contact with plants and soils. Case presentation: An immunocompetent male presented with a history of penetrating ocular trauma that had evolved to infectious endophthalmitis, which was refractory to different antibiotic treatments. No micro-organisms were isolated from repeated conjunctival smear and corneal scraping cultures between the ocular trauma (August 2014) and the endophthalmitis diagnosis (November 2015). After this period, N. nova sensu stricto was isolated in aqueous humour aspirate. Treatment was adjusted and clinical improvement was obtained after an adequate microbiological procedure, including an optimal sampling and an antimicrobial-susceptibility testing report. Conclusion: Nocardia identification to the species level and performance of antimicrobial-susceptibility tests are both essential tools for treatment adjustment and clinical improvement

Resumen ejecutivo de la Declaración de consenso del Grupo de Estudio de la Infección en el Trasplante (GESITRA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y la Organización Nacional de Trasplantes (ONT) sobre los criterios de selección de donantes de órganos sólidos en relación con las enfermedades infecciosas

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.This work was supported by GESITRA/SEIMC, ONT and‘Plan Nacional de I+D+I’ and Instituto de Salud Carlos III(Fondo de Investigaciones Sanitarias 12/02269 and ProyectoIntegrado de Excelencia 13/00045), Subdirección General de Redesy Centros de Investigacion Cooperativa, Spanish Ministry of Econ-omy and Competitiveness, Spanish Network for Research inInfectious Diseases (REIPI RD16/0016), co-financed by the Euro-pean Development Regional Fund A way to achieve Europe

Healthcare-associated pneumonia: a prospective study in Spain

Objective: The aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP). Methods: A 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: "S. pneumoniae", "MRSA", "Others" and "Unknown". Patients were followed up 30 days after discharge. Results: A total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%): S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p<0.05), other chronic respiratory diseases, inhaled corticosteroids (p <0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia. Conclusions: The etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.Objetivo: Describir las características epidemiológicas y factores relacionados con la neumonía asociada a cuidados sanitarios (NACS) causada por Streptococcus pneumoniae y Staphylococcus aureus resistente a meticilina (SARM). Pacientes y métodos: Estudio epidemiológico observacional prospectivo de casos a 3 años en siete hospitales españoles. Se recogieron las características microbiológicas y de los pacientes y sus resultados y se clasificaron en función del patógeno causante en 4 categorías: ?S. pneumoniae?, ?SARM?, ?Otros? y ?Desconocido?. Al alta, se realizó un seguimiento de 30 días. Resultados: Se incluyeron 258 (84,6%) pacientes (170 hombres [65.9%]; edad media 72,4 años ± 15 años (95% IC [70,54-74,25]). La etiología de la neumonía se identificó en 73 casos (28,3%):S. pneumoniae en 35 pacientes (13,6%), SARM en 8 (3,1%) y otros microorganismos en 30 pacientes (11,6%). Hubo diferencias significativas en tasas de enfermedad pulmonar obstructiva crónica (p < 0,05), tratamiento antibiótico previo (p < 0,05), otras enfermedades respiratorias crónicas, corticoides inhalados (p < 0,01) y linfoma (p < 0,05) entre los cuatro grupos. Los pacientes con NACS causada por SARM recibieron tratamiento antibiótico previo en mayor medida (87,5%). Treinta y tres (12,8%) pacientes murieron durante la hospitalización; en 27 (81,2%) debido a la neumonía. Conclusiones: Se identificó la etiología de la NACS en solo un cuarto de los pacientes, siendo S. pneumoniae el patógeno más frecuente. En los pacientes con enfermedades respiratorias crónicas fue más frecuente la NACS causada por SARM. La muerte tras el alta hospitalaria se relacionó con la neumonía en la mayoría de los casos

Efficiency of a self-administered outpatient parenteral antimicrobial therapy (s-opat) for infectiveendocarditis within the context of a shortened hospital admission based on hospital at homeprogram

OBJECTIVE: This study aimed to evaluate the efficiency of treatment of infectious endocarditis (IE) via Self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT) supported by a shortening hospital admission program in a hospitalization-at-home unit (HAH), including a short review of the literature. METHODS: Ambispective cohort study of 57 episodes of IE in 54 patients treated in an HAH unit between 1988 and 2014 who receive S-OPAT after prior intra-hospital clinical stabilization. Characteristics of each episode of IE, safety and efficiency of the care model, were analyzed. RESULTS: Forty-three (76%) patients were males with a median age of 61 years (SD = 16.5). A total of 37 (65%) episodes affected the native valve (42% the aortic valve). In 75%, a micro-organism was isolated, of which 88% were Gram-positive bacteria. No deaths occurred during HAH program, clinical complications appeared in 30% of episodes, only 6 patients were re-admitted to hospital although no patient died. In the 12 months' follow-up 3 cases had a recurrence. The average cost of a day stay in HAH was €174 while in traditional cardiology hospitalization was €1100. The total average cost of treatment of each episode of IE managed entirely in hospital was calculated as €54,723. Application of the S-OPAT model based on HAH meant a cost reduction of 32.72%. CONCLUSIONS: In suitably selected patients, treatment of IE based on S-OPAT supported by a shortening hospital admission care program by means of referral to a HAH unit is a safe and efficient care model which entails a significant cost saving for the public healthcare system