Two mutually related pandemics are ongoing worldwide: the COVID-19 and antimicrobial resistance pandemics. This study aims to evaluate the impact of COVID-19 on multi-drug-resistant Gram-negative bacteria (MDR-GN) bloodstream infections (BSIs) in a single intensive care unit (ICU). We conducted a retrospective study including patients admitted to the ICU, reorganized for COVID-19 patients’ healthcare, with at least one confirmed MDR-GN BSI during 2019–2020. We compared clinical and microbiological features, incidence density, antibiotic therapy and mortality rate in pre- and during-COVID-19 pandemic periods. We estimated the impact of COVID-19 on mortality by means of univariate Cox regression analyses. A total of 46 patients were included in the study (28 non-COVID-19/18 COVID-19). Overall, 63 BSI episodes occurred (44/19), and non-COVID-19 patients had a higher incidence of MDR-GN BSIs and were more likely to present K. pneumoniae BSIs, while the COVID-19 group showed more A. baumannii BSIs with higher per pathogen incidence. COVID-19 patients presented more critical conditions at the BSI onset, a shorter hospitalization time from BSI to death and higher 30-day mortality rate from BSI onset. COVID-19 and septic shock were associated with 30-day mortality from MDR-GN BSIs, while early active therapy was a protective factor. In conclusion, COVID-19 showed a negative impact on patients with MDR-GN BSIs admitted to the ICU.

Gram-negative bacilli septic thrombosis (GNB-ST) represents a subtle and often misleading condition, potentially fatal if not recognized early and requiring prolonged antimicrobial therapy and anticoagulation. Herein, reported for the first time, is a very challenging case of Klebsiella producing carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) ST unresponsive to ceftazidime/avibactam (CZA) relapsed first with meropenem/vaborbactam (MVB) monotherapy and subsequently cured with MVB plus fosfomycin (FOS) combination. The present case highlights the possibility of CZA underexposure on the infected thrombus and the risk of in vivo emergence of CZA resistance in the setting of persistent bacteremia and sub-optimal anticoagulation. Pharmacokinetic analyses showed that both MVB and FOS were in the therapeutic range. In vitro studies demonstrated a high level of MVB + FOS synergism that possibly allowed definitive resolution of the endovascular infection.

Bloodstream infections still constitute an outstanding cause of in-hospital morbidity and mortality, especially among critically ill patients. Follow up blood cultures (FUBCs) are widely recommended for proper management of Staphylococcus aureus and Candida spp. infections. On the other hand, their role is still a matter of controversy as far as Gram negative bacteremias are concerned. We revised, analyzed, and commented on the literature addressing this issue, to define the clinical settings in which the application of FUBCs could better reveal its value. The results of this review show that critically ill patients, endovascular and/or non-eradicable source of infection, isolation of a multi-drug resistant pathogen, end-stage renal disease, and immunodeficiencies are some factors that may predispose patients to persistent Gram negative bacteremia. An analysis of the different burdens that each of these factors have in this clinical setting allowed us to suggest which patients’ FUBCs have the potential to modify treatment choices, prompt an early source control, and finally, improve clinical outcome.

The overall low-quality evidence concerning the clinical benefits of different antibiotic regimens for the treatment of infective endocarditis (IE), which has made it difficult to strongly support or reject any regimen of antibiotic therapy, has led to a discrepancy between the available guidelines and clinical practice. In this complex scenario, very recently published guidelines have attempted to fill this gap. Indeed, in recent years several antimicrobials have entered the market, including ceftobiprole, ceftaroline, and the long-acting lipoglycopeptides dalbavancin and oritavancin. Despite being approved for different indications, real-world data on their use for the treatment of IE, alone or in combination, has accumulated over time. Furthermore, an old antibiotic, fosfomycin, has gained renewed interest for the treatment of complicated infections such as IE. In this narrative review, we focused on new antimicrobials and therapeutic strategies that we believe may provide important contributions to the advancement of Gram-positive IE treatment, providing a summary of the current in vitro, in vivo, and clinical evidence supporting their use in clinical practice.