Resistance to beta-lactams in Gram-negative bacilli: relevance and potential therapeutic alternatives.

The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health problem that entails high morbidity and mortality: the antibiotic multi-drug resistance. In 2017 and 2019, the World Health Organization published a list of urgent threats and priorities in the context of drug resistance, which only included Gram-negative bacteria and specially focused on carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem and third generation cephalosporin-resistant Enterobacteriaceae. This scenario emphasizes the need of developing and testing new antibiotics from different families, such as new beta-lactams, highlighting cefiderocol and its original mechanism of action; new beta-lactamase inhibitors, with vaborbactam or relebactam among others; new quinolones such as delafloxacin, and also omadacycline or eravacycline, as members of the tetracycline family. The present work reviews the importance and impact of Gram-negative bacterial infections and their resistance mechanisms, and analyzes the current therapeutic paradigm as well as the role of new antibiotics with a promising future in the era of multi and pan-drug resistance.

Etiology, diagnosis, and management of pneumonia in immunosuppressed patients.

Patients with a compromised immune system suffer a wide variety of insults. Pulmonary complications remain a major cause of both morbidity and mortality in immunocompromised patients. When such individuals present with radiographic infiltrates, the clinician faces a diagnostic challenge. The differential diagnosis in this setting is broad and includes both infectious and non-infectious conditions. Evaluation of the immunocompromised host with diffuse pulmonary infiltrates can be difficult, frustrating, and time-consuming. This common and serious problem results in significant morbidity and mortality, approaching 90%. Infections are the most common causes of both acute and chronic lung diseases leading to respiratory failure. Non-invasive diagnostic methods for evaluation are often of little value, and an invasive procedure (such as bronchoalveolar lavage, transbronchial biopsy or even open lung biopsy) is therefore performed to obtain a microbiologic and histologic diagnosis. Bronchoscopy allows certain identification of some aetiologies, and often allows the exclusion of infectious agents. Early use of computed tomography scanning is able to demonstrate lesions missed by conventional chest X-ray. However, even when a specific diagnosis is made, it might not impact patient's overall survival and outcomes.

Tedizolid: new data and experiences for clinical practice.

The most relevant information on the clinical uses of tedizolid from studies published in the last 18 months is presented in this brief review. The most important data indicate better tolerance and safety profile of long-term therapeutic regimes in off-label indications, such as osteoarticular infections and those caused by mycobacteria. Its lower risk of hazardous interactions compared to linezolid should be emphasized. Furthermore, tedizolid in its combination with rifampicin shows a more favourable way of acting as demonstrated in vitro and in vivo studies. A recent trial also opens the door for its potential use in nosocomial pneumonia caused by Gram-positive bacteria.

[Role of cefditoren in the treatment of community skin and soft tissue infections: revisiting the evidence]. / Papel de cefditoreno en el tratamiento de las infecciones comunitarias de piel y tejidos blandos: revisando la evidencia.

Cefditoren pivoxil is a third-generation oral cephalosporin with extended spectrum against Gram-negative, Gram-positive, and several anaerobic microorganisms, including those frequently implicated in skin and soft tissue infections (SSTI). Despite the fact that there are no approved breakpoint criteria for cefditoren susceptibility, many pharmacokinetic and pharmacodynamic studies reassert cefditoren as a good oral antibiotic for the treatment of SSTI. Regarding patients with SSTI, including those infections caused by Staphylococcus aureus y Streptococcus pyogenes, cefditoren showed high cure rates when compared to other oral cephalosporins.

A clinical predictive model of candidaemia by Candida auris in previously colonized critically ill patients.

OBJECTIVES: Candida auris is an emerging multidrug-resistant fungus that has been associated with nosocomial outbreaks with high rates of mortality and transmission. The aim of this study was to perform a retrospective cohort analysis of risk factors and to build a scoring method for estimating the risk of candidaemia in colonized critically ill patients. METHODS: We performed a retrospective observational cohort study of patients aged ≥15 years colonized by C. auris in the 3-year period between March 2016 and March 2019. Epidemiological, clinical, laboratory and microbiological data were collected. We developed a predictive model for candidaemia using elastic net multivariable logistic regression techniques, assessed its discriminative capacity, and internally validated it using bootstrap resampling. RESULTS: Two-hundred and six patients were enrolled in the cohort for derivation and internal validation. Thirty-seven out of 206 patients developed candidaemia. Total parenteral nutrition was the foremost risk factor (adjusted OR 3.73); previous surgery (adjusted OR 1.03), sepsis (adjusted OR 1.75), previous exposure to antifungal agents (adjusted OR 1.17), arterial catheters (adjusted OR 1.46), central venous catheters (adjusted OR 1.21), presence of advanced chronic kidney disease (adjusted OR 1.35) and multifocal colonization (adjusted OR of unifocal colonization 0.46) were proven to be independent predictors of candidaemia in our cohort. The corresponding area under the curve (AUC) of the elastic net regularized predictive model was 0.89 (95%CI 0.826; 0.951). After performing the internal validation by generating 500 bootstrap replications, the model still showed great accuracy, with a resulting AUC of 0.84. CONCLUSION: Our study provides evidence on the independent predisposing factors for candidaemia. It may help predict its estimated risk and may identify a high-risk population that could benefit from early or prophylactic antifungal treatment after external validation in other cohorts.

First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study.

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.

Trasplante de médula ósea con células de sangre periférica en meduloblastoma recidivado. A propósito de un caso / Transplantation of bone marrow with peripheral blood cells in a recurrent medulloblastoma. Repor of a case

Propósito: Descripción de un caso de recidiva de meduloblastoma tratado con quimioterapia intensiva. Material y métodos: Varón de 23 años, intervenido quirúrgicamente de meduloblastoma. El paciente presenta una recidiva que afecta huesos y médula ósea. La quimioterapia fue consolidada con autotrasplante de médula ósea con células de sangre periférica. La remisión se mantuvo durante 3 años. Resultados: Los autores realizan una revisión de la literatura sobre la eficacia de la quimioterapia y sus indicaciones en meduloblastoma. Conclusiones: Los estudios publicados incluyen pocos pacientes o con escaso seguimiento, pero concuerdan con la evolución de nuestro paciente. Confirman la excepcionalidad de una recidiva en hueso con integridad del Sistema Nervioso central y de la reiterada negatividad de la gammagrafía ósea (AU)

Suspected extragonadal germ-cell cancer syndrome presenting with an orbital mass and elevation of serum CEA, CA 19-9 and CA50 levels.

Patients with extragonadal germ-cell cancer syndrome (EGCCS) represent a subgroup of patients with poorly differentiated carcinoma or adenocarcinoma of an unknown primary site for whom potentially curative therapy is available. We report the case of a young man presenting an orbital tumor and high serum levels of CEA, CA 19-9 and CA50 for whom an initial diagnosis of metastatic poorly differentiated carcinoma was made. Suspecting EGCCS, he was treated as for a germ-cell tumor. While in treatment, he underwent residual orbital mass resection, and the histologic diagnosis was embryonal carcinoma based on alpha-fetoprotein immunoperoxidase staining. We discuss the rare location at diagnosis, the impressive increase in the commonly considered gastrointestinal markers that he showed, and the potential utility of these markers for such patients.