Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study.

BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. OBJECTIVES: To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). METHODS: A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. RESULTS: One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. CONCLUSIONS: Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

Good's syndrome and pure white cell aplasia complicated by cryptococcus infection: A case report and review of the literature.

Thymomas can present with a variety of paraneoplastic manifestations, mostly of autoimmune origin, including Good's syndrome when there is associated hypogammaglobulinemia. Although pure red cell aplasia is a recognised complication of thymoma, selective white cell aplasia is very rare, particularly in Good's syndrome. Lethal opportunistic infections are a feature of Good's syndrome, usually occurring in those patients with associated severe T lymphocyte defects. Although the cryptococcus is a recognised fungal pathogen in patients with other causes of CD4+ T cell lymphopenia, surprisingly this complication has not been reported in patients with Good's syndrome. We now describe a 70 year old man with Good's syndrome and pure white cell aplasia who presented with disseminated cryptococcosis, and provide an up-to-date review of the relevant literature. Despite meningeal involvement our patient recovered after combined treatment with intravenous globulin, granulocyte stimulating growth, corticosteroids and antifungal therapy.

Infectious complications in patients with lung cancer.

Infections remain a part of the natural course of cancer. During the course of their disease, patients with lung cancer frequently present with an infection that can ultimately be fatal. Pathogenesis of infectious syndromes is usually determined by the underlying disease, as well as, the iatrogenic manipulations that occur during its management. Hence, lung cancer infections include lower respiratory tract infections in the context of COPD, aspiration, obstruction and opportunistic infections due to immunosuppression. Moreover, treatment-related infectious syndromes including post operative pneumonia, febrile neutropenia and superimposed infection following radiation/chemotherapy toxicity is common. Importantly, diagnosis of infection in the febrile lung cancer patient is challenging and requires a high index of suspicion in order to distinguish from other causes of fever, including malignant disease and pulmonary embolism. Prompt initiation of treatment is pivotal to avoid increased mortality. Careful consideration of infection pathogenesis can predict most likely pathogens and guide antibiotic management, thus, ensuring most favourable outcome.

Clinical outcomes in vaccinated and unvaccinated patients with COVID-19: a population-based analysis.

OBJECTIVE: Real-life data for vaccination against COVID-19 are sorely needed. This was a population-based analysis aiming at investigating the hospitalization risk for COVID-19 of 98,982 subjects and compare features of vaccinated and unvaccinated patients. PATIENTS AND METHODS: Hospitalized patients with COVID-19 between 01/07/2021 and 11/02/2022 were included in the study. RESULTS: 582 patients were included in the analysis [males: 58.6% (n=341), vaccinated patients: 28.5% (n=166), unvaccinated patients: 71.5% (n=416)]. Median age of vaccinated patients was significantly higher compared to median age of unvaccinated [74.0 (95% CI: 72.0-77.0) vs. 59.0 (95% CI: 57.0-62.0), p=0.0001]. Mean latency time (±SD) from the second dose to hospitalization was 5.7±2.6 months. Between 01/07/2021 and 01/12/2021, unvaccinated subjects had higher risk for hospitalization compared to vaccinated [HR: 2.82, 95% CI: 2.30-3.45, p<0.0001]. Between 02/12/2021 and 11/02/2022, unvaccinated subjects presented with higher risk for hospitalization than subjects that had received booster dose [HR: 2.07, 95% CI: 1.44-2.98, p=0.005], but not than subjects that got two doses. Median value of hospitalization days was higher in unvaccinated patients compared to vaccinated [7.0 (95% CI: 7.0-8.0) vs. 6.0 (95% CI: 5.0-7.0), p=0.02]. Finally, age-adjusted analysis showed that hospitalized unvaccinated patients presented with significantly higher mortality risk compared to hospitalized vaccinated patients [HR: 2.59, 95% CI: 1.69-3.98, p<0.0001]. CONCLUSIONS: Vaccination against COVID-19 remains the best way to contain the pandemic. There is an amenable need for booster dose during the omicron era.