Predictive score of haematological toxicity in patients treated with linezolid.

OBJECTIVE: The aims of our study were to determine the factors associated with developing haematological toxicity (HT) in patients taking linezolid (LZD), to develop a predictive model of HT in these patients, and to evaluate factors associated with 30-day mortality. METHODS: This was an observational retrospective cohort study of patients treated for at least 5 days with LDZ in 2015. Demographic, clinical and analytical data were collected. Development of HT was defined as a 25% platelet count decrease between the basal count and the 1-week lab test. RESULTS: Five hundred forty-nine patients were finally included, mean age was 73.3 (SD 15.4) years, and 303 (55.2%) were men. One hundred seventy-five (30.1%) patients achieved HT criteria during treatment with LZD and 41 (7.5%) died. The final model included the presence of cerebrovascular disease (2 points), moderate or severe liver disease (2 points), renal failure (2 points) and basal platelet count less than 90,000/mm3 (8 points). This new model showed an AUC of 0.711 (IC 95% 0.664-0.757; p < 0.001) to predict the development of HT. The probability of HT based on this classification was 6.2, 29.9 and 76.5% for low (0-4 points), intermediate (5-10 points) and high risk (>10 points), respectively. The independent variables associated with 30-day mortality were metastatic solid tumor, lymphoma, age >75 years and HT. CONCLUSION: This score could help in the identification of patients with high risk for HT and assess the use of an antibiotic other than LZD, an important issue considering its relation with 30-day mortality observed in our study.

Candent issues in pneumonia. Reflections from the Fifth Annual Meeting of Spanish Experts 2023.

Pneumonia is a multifaceted illness with a wide range of clinical manifestations, degree of severity and multiple potential causing microorganisms. Despite the intensive research of recent decades, community-acquired pneumonia remains the third-highest cause of mortality in developed countries and the first due to infections; and hospital-acquired pneumonia is the main cause of death from nosocomial infection in critically ill patients. Guidelines for management of this disease are available world wide, but there are questions which generate controversy, and the latest advances make it difficult to stay them up to date. A multidisciplinary approach can overcome these limitations and can also aid to improve clinical results. Spanish medical societies involved in diagnosis and treatment of pneumonia have made a collaborative effort to actualize and integrate last expertise about this infection. The aim of this paper is to reflect this knowledge, communicated in Fifth Pneumonia Day in Spain. It reviews the most important questions about this disorder, such as microbiological diagnosis, advances in antibiotic and sequential therapy, management of beta-lactam allergic patient, preventive measures, management of unusual or multi-resistant microorganisms and adjuvant or advanced therapies in Intensive Care Unit.

[Usefulness of the MPB-INFURG-SEMES model to predict bacteremia in the patient with solid tumor in the Emergency Department]. / Utilidad del modelo MPB-INFURG-SEMES para predecir bacteriemia en el paciente con neoplasia sólida en el Servicio de Urgencias.

OBJECTIVE: To analyse a new risk score to predict bacteremia (MPB-INFURG-SEMES) in the patients with solid tumor attender for infection in the emergency departments (ED). METHODS: Prospective, multicenter observational cohort study of blood cultures (BC) obtained from adult patients with solid neoplasia treated in 63 EDs for infection from November 1, 2019, to March 31, 2020. The predictive ability of the model was analyzed with the area under the Receiver Operating Characteristic curve (AUC-ROC). The prognostic performance for true bacteremia was calculated with the chosen cut-off for getting the sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: A total of 857 blood samples wered cultured. True cases of bacteremia were confirmed in 196 (22.9%). The remaining 661 cultures (77.1%) wered negative. And, 42 (4.9%) were judged to be contaminated. The model's area under the receiver operating characteristic curve was 0.923 (95% CI,0.896-0.950). The prognostic performance with a model's cut-off value of ≥ 5 points achieved 95.74% (95% CI, 94,92-96.56) sensitivity, 76.06% (95% CI, 75.24-76.88) specificity, 53.42%(95% CI, 52.60-54.24) positive predictive value and 98.48% (95% CI, 97.66- 99.30) negative predictive value. CONCLUSIONS: The MPB-INFURG-SEMES score is useful for predicting bacteremia in the adults patients with solid tumor seen in the ED.

Nosocomial pneumonia: Current etiology and impact on antimicrobial therapy.

Nosocomial pneumonia is an infection with high clinical impact and high morbimortality in which Pseudomonas aeruginosa plays a priority role, especially in the critically ill patient. Conventional antipseudomonal treatments, historically considered as standard, are currently facing important challenges due to the increase of antimicrobial resistance. In recent years, new antimicrobials have been developed with attractive sensitivity profiles and remarkable efficacy in clinical scenarios of nosocomial pneumonia including bacteremia, mechanical ventilation, infections with multidrug-resistant organisms or situations of therapeutic failure. This new evidence underscores the need to update current clinical guidelines for the antimicrobial treatment of nosocomial pneumonia, especially in the most critically ill patients.

Risk of severe COVID in solid organ transplant recipient.

Despite the fact that COVID is today not a life-threat for the general population, recipients of solid organ transplantation should be viewed as a high risk group for severe COVID. Repetitive doses of SARS-CoV-2 vaccine still fail to protect SOT recipients from infection, disease or even death caused by COVID. A more frequent need for medical care may initially place these patients at greater chances of SARS-CoV-2 infection. Immunosuppression after engrafting and underlying medical conditions that led to the practice of SOT contribute to more risk of severe infection. Immunosuppression also blunts the intensity of humoral and cellular responses after vaccination, even when several booster doses have been administered. Still, vaccination is the best strategy to prevent a fatal outcome in case of SARS-CoV-2 infection, with a particular reduction in mortality. SOT recipients should be considered a high-risk population that need yearly SARS-CoV-2 vaccination.

Therapeutic strategy in the transplanted patient.

The SARS-CoV-2 infection prognosis has dramatically changed as a result of population vaccination and the surge of omicron. However, there are still specific populations at risk of progression to severe diseases that require hospitalization or even at risk of death. The kidney transplant population is one of them. Consequently, when compatible symptoms appear, an early diagnosis should be sought in order to start specific antiviral treatment as soon as possible to avoid clinical deterioration of the patient. Antivirals have shown, in transplant patients, a decrease in the rate of hospitalization and death, especially with their early administration.

Reduction in the risk of progression of solid organ transplant recipients infected by SARS-CoV-2 treated with monoclonal antibodies.

Recipients of solid organ transplants (SOT) are at higher risk of infection by SARS-CoV-2 virus especially due to chronic immunosuppression therapy and frequent multiple comorbid conditions. COVID-19 is a potentially life-threatening disease in SOT recipients, with an increased likelihood of progressing to severe disease, with the need of hospitalization, admission to the intensive care unit (ICU) and mechanical ventilatory support. This article presents an updated review of different aspects related to the outcome of COVID-19 in SOT recipients. In nvaccinated SOT recipients, COVID-19 is associated with a high mortality rate, in-patient care and ICU admission, and impaired graft function or rejection in severe disease. In vaccinated SOT recipients even after full vaccination, there is a reduction of the risk of mortality, but the course of COVID-19 may continue to be severe, influenced by the time from transplant, the net state of immunosuppression and having suffered graft rejection or dysfunction. SOT recipients develop lower immunity from mRNA vaccines with suboptimal response. Treatment with mAbs provides favorable outcomes in non-hospitalized SOT recipients at high risk for severe disease, with lower rates of hospitalization, emergency department visits, ICU care, progression to severe disease, and death. However, broad vaccination and therapeutic options are required, particularly in light of the tendency of the SARS-CoV-2 virus to adapt and evade both natural and vaccine-induced immunity.

[Ability of qSOFA1-lactate to predict 30-day mortality in patients seen for infection in the Emergency Department]. / Capacidad del qSOFA1-lactato para predecir mortalidad a 30 días en los pacientes atendidos por infección en urgencias.

OBJECTIVE: To evaluate lactate and the Quick Sepsis-Related Organ Failure Assessment (qSOFA) and compare their ability to predict 30-day mortality in patients treated for infection in emergency departments (ED). METHODS: Prospective multicenter observational cohort study. We enrolled a convenience sample of patients aged 18 years or older attended in 71 Spanish ED from October 1, 2019, to March 31, 2020. Each model's predictive power was analyzed with the area under the receiver operating characteristic curve (AUC), and its values of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative (NPV). RESULTS: A total of 4439 patients with a mean (SD) age of 18 years were studied; 2648 (59.7%) were men and 459 (10.3%) died within 30 days. For 30-day mortality, the AUC-COR obtained with the qSOFA = 1 model plus 2 mmol/l lactate was 0.66 (95% CI, 0.63-0.69) with Se: 68%, Es: 70% and NPV:92%, while qSOFA = 1 obtained AUC-COR of 0.52 (95% CI, 0.49-0.55) with a Se:42%, Es:64% and NPV:90%. CONCLUSIONS: To predict 30-day mortality in patients presenting to the ED due to an episode of infection, the qSOFA =1 + lactate≥2 mmol/L model significantly improves the predictive power achieved individually by qSOFA1 and becomes very similar to qSOFA≥2.

Value of syndromic panels in the management of severe community-acquired pneumonia.

Community-acquired pneumonia requiring hospital admission is a prevalent and potentially serious infection, especially in high-risk patients (e.g., those requiring ICU admission or immunocompromised). International guidelines recommend early aetiological diagnosis to improve prognosis and reduce mortality. Syndromic panels that detect causative pathogens by molecular methods are here to stay. They are highly sensitive and specific for detecting the targets included in the test. A growing number of studies measuring their clinical impact have observed increased treatment appropriateness and decreased turnaround time to aetiological diagnosis, need for admission, length of hospital stay, days of isolation, adverse effects of medication and hospital costs. Its use is recommended a) per a pre-established protocol on making the diagnosis and managing the patient, b) together with an antimicrobial stewardship programme involving both the Microbiology Service and the clinicians responsible for the patient, and c) the final evaluation of the whole process. However, we recall that microbiological diagnosis with traditional methods remains mandatory due to the possibility that the aetiological agent is not included among the molecular targets and to determine the antimicrobial susceptibility of the pathogens detected.

Ceftolozane-tazobactam in nosocomial pneumonia.

Ceftolozane is a potent antimicrobial against Pseudomonas aeruginosa, including carbapenem-resistant and multidrug-resistant strains, and is also active against Enterobacteriaceae. It MIC (minimal inhibitory concentration) and MPC (mutant preventive concentration) are close together, allowing to avoid the mutant selection window specifically in the treatment of Pseudomonas aeruginosa infection. The molecule is time-dependent and stable when reconstituted at room temperature, facilitating safe and effective dosage optimization in frail and critically ill patients. It has been shown to be non-inferior to meropenem in the treatment of nosocomial infection in the ASPECT-NP study but superior in post-hoc studies in the subgroup of patients with ventilator-associated pneumonia, without the emergence of resistance during treatment. It is FDA approved at a dose of 3 g every 8 hours in the treatment of nosocomial pneumonia (HABP/VABP) in adults.

[New predictive models of bacteremia in the emergency department: a step forward]. / Nuevos modelos predictivos de bacteriemia en el servicio de urgencias: un paso adelante.

The care of patients with a suspected infectious process in hospital emergency department (ED) has increased in the last decade to account for around 15-20% of all daily care. In the initial evaluation of these patients, samples are taken for the different microbiological studies in 45% of the cases, where obtaining blood cultures (BC) predominates, in 14.6% of all of them. The diagnostic yield of these BC is highly variable (2-20%). The most frequent suspected or confirmed foci or infectious processes of true bacteremia (TB) in the ED are urinary tract infection (45%) and respiratory infection (25%). For all these reasons, the suspicion and confirmation of TB has a relevant diagnostic and prognostic significance and requires changing some of the most important decisions to be made in the ED. Among others, indicate discharge or admission, extract BC and administer the appropriate and early antimicrobial. The intention of this review is to highlight the scientific evidence published in the last five years, clarify the current controversies and compare the ability to predict bacteremia of the latest predictive models published since 2017 with those already existing on that date, year in which a review was published that left open the proposal to continue searching for a model with adequate performance for ED. And so, based on it, generate different recommendations that help define the role that these models or scales can have in improving the indication for obtaining BC, as well as in the immediate making of other diagnostic-therapeutic decisions (administration early and appropriate antibiotic treatment, request for complementary tudies and other microbiological samples, intensity of hemodynamic support, need for admission, etc.).

Models for bacteraemia risk prediction. Clinical implications.

Bacteraemia has important consequences for the patient, as it is associated with worse clinical outcomes. On the other hand, unnecessarily obtaining samples for blood cultures increases costs and the workload in the microbiology laboratory. Its diagnosis implies a time delay, but decisions about start antibiotic treatment, discharge, or admits the patient must be taken during the first attention and, therefore, before known the blood cultures results. This manuscript reviews the different strategies based on clinical scores and biomarkers that are useful for predicting bacteraemia and improving initial decision-making.

COVID-19 in donation and transplant.

SARS-CoV-2 infection has had a major impact on donation and transplantation. Since the cessation of activity two years ago, the international medical community has rapidly generated evidence capable of sustaining and increasing this neccesary activity. This paper analyses the epidemiology and burden of COVID-19 in donation and transplantation, the pathogenesis of the infection and its relationship with graft-mediated transmission, the impact of vaccination on donation and transplantation, the evolution of donation in Spain throughout the pandemic, some lessons learned in SARS-CoV-2 infected donor recipients with positive PCR and the applicability of the main therapeutic tools recently approved for treatment among transplant recipients.

[Community-acquired pneumonia: selection of empirical treatment and sequential therapy. SARS-CoV-2 implications]. / Neumonía comunitaria: selección del tratamiento empírico y terapia secuencial. Implicaciones del SARS-CoV-2.

Pneumonia is a major cause of global mortality in developed countries. The adequacy of the antibiotic treatment is essential for the good evolution of the patients. When selecting the antimicrobial, the severity of the patient, the characteristics of the antibiotics, and the profile of the patient to be treated should be considered. Recommendations for the selection of antibiotic treatment may differ between the patient who requires admission and the one who can be treated as outpatient. Beta-lactams, fluoroquinolones, and macrolides are the most widely used antimicrobials in this last circumstance. However, not all are the same in terms of efficacy, safety and ecological impact. This review delves into the aforementioned aspects to improve decision-making and offers concrete recommendations for the selection of antibiotic treatment. Likewise, it includes recommendations for performing sequential therapy. Finally, a brief review is made about the impact of SARS-CoV-2 infection on this pathology.

Infection and infectivity: Utility of rapid antigen tests for the diagnosis of COVID-19.

Detection of SARS-CoV-2 proteins is commercially available in the form of lateral-flow rapid antigen test for the point-of-care diagnosis of COVID-19. This platform has been validated for symptomatic and asymptomatic individuals, for diagnosis or screening, and as part of single or sequential diagnostic strategies. Although in general less sensitive than amplification techniques, antigen tests may be particularly valid during the first days of symptoms and to detect individuals with greater viral load, thereby with enhanced chances of viral transmission. The simplicity of antigen tests make them very suitable to discard infection in settings with low pretest probability, and to detect infection in case of higher chances of having COVID-19.

Seroprevalence and Trends of HTLV-1/2 among Blood Donors of Santo Domingo, Dominican Republic, 2012-2017.

OBJECTIVE: Being a Caribbean country, the Dominican Republic is considered endemic for HTLV-1. Viral screening in blood banks is recommended for this blood borne infection. The purpose of this work is to analyze the seroprevalence and trends of HTLV-1/2 in the Dominican Republic blood donors; it is focused on Santo Domingo, the capital of the country, which has the largest blood donation activity. We also aim at comparing our findings with published data from neighboring countries. METHODS: We performed a retrospective cross-sectional study of 10 blood centers of Santo Domingo, which reported HTLV and the other blood-transmitted infections in full. They represent more than 40% of the province's blood donations. Annual seroprevalence of HTLV-1/2, period prevalence (2012-2017), and time trend were determined. RESULTS: A total of 352,960 blood donations were evaluated. The HTLV-1/2 period prevalence was 0.26% (929/352,960)(95% CI: 0.24-0.28%). We also found a marked predominance of replacement donation (90.4%) in comparison to voluntary contributions (9.6%). Therefore, this blood donor study may provide clues on the general prevalence of the infection. CONCLUSIONS: Seroprevalence of HTLV-1/2 in blood donors of Santo Domingo, Dominican Republic, showed a relatively low and steady trend in the studied period.

In vitro activity of imipenem/relebactam against Gram-negative clinical isolates in two Spanish tertiary hospitals.

OBJECTIVE: The aim of this study was to analyze the activity of the imipenem-relebactam combination (IMI/REL) against a collection of multidrug-resist Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates. METHODS: The study was conducted in two tertiary hospitals in Spain and included 192 clinical isolates of these 3 genera (139 resistant and 53 susceptible to IMI). The MICs for IMI with and without REL (at a fixed concentration of 4 mg/L) were determined by a standard broth microdilution method according to international recommendations. RESULTS: All IMI-susceptible E. coli strains were also susceptible to IMI/REL. Enterobacterales resistant to IMI due to the production of carbapenemases, the MIC50 and MIC90 decreased from 64/256 with IMI to 8/64 mg/L with IMI/REL. This high activity was principally detected among isolates with KPC enzymes. Enterobacterales with class B carbapenemases, P. aeruginosa carrying VIM carbapenemase and A. baumannii strains showed no changes on IMI MIC50 or MIC90 after adding REL. Among P. aeruginosa strains without carbapenemase the MIC for IMI/REL was reduced between 1 to 5 dilutions. CONCLUSIONS: IMI/REL showed high activity against the strains that carry Klebsiella pneumoniae carbapenemase (KPC) and against carbapenem-resistant P. aeruginosa unrelated to the VIM enzyme, mainly AmpC beta lactamase associated with impermeability. Against strains carrying oxacillinase 48 (OXA-48) associated with extended-spectrum beta-lactamase (ESBL), IMI/REL presented activity only slightly better than IMI and had no beneficial effect superior to IMI against A. baumannii.

Approach to COVID-19 pandemic management in Madrid. Chronic of a year.

After more than a year of pandemic, the international medical community has changed the perception of fear to one of respect for SARS-COV-2. This has been the consequence of the integral study of all the dimensions of the disease, from viral recombinant capacity to transmissibility, diagnosis, care and prevention. This document summarizes the main strategic lines of study and approach to the pandemic in Madrid.

[Usefulness of the 5MPB-Toledo model to predict bacteremia in patients with community-acquired pneumonia in the Emergency Department]. / Utilidad del modelo 5MPB-Toledo para predecir bacteriemia en el paciente con neumonía adquirida en la comunidad en el Servicio de Urgencias.

OBJECTIVE: To analyse a new risk score to predict bacteremia in the patients with Community-acquired Pneumonia (CAP) in the emergency departments. METHODS: Prospective and multicenter observational cohort study of the blood cultures ordered in 74 Spanish emergency departments for patients with CAP seen from November 1, 2019, to March 31, 2020. The predictive ability of the model was analyzed with the area under the Receiver Operating Characteristic curve (AUC-ROC). The prognostic performance for true bacteremia was calculated with the chosen cut-off for getting the sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: A total of 1,020 blood samples wered cultured. True cases of bacteremia were confirmed in 162 (15.9%). The remaining 858 cultures (84.1%) wered negative. And, 59 (5.8%) were judged to be contaminated. The model´s area under the receiver operating characteristic curve was 0.915 (95% CI, 0.898-0.933). The prognostic performance with a model´s cut-off value of ≥ 5 points achieved 97.5% (95% CI, 95.1-99.9) sensitivity, 73.2% (95% CI, 70.2-76.2) specificity, 40.9% (95% CI, 36.4-45.1) positive predictive value and 99.4% (95% CI, 99.1-99.8) negative predictive value. CONCLUSIONS: The 5MPB-Toledo score is useful for predicting bacteremia in the patients with CAP seen in the emergency departments.