Background Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy. Methods A multicenter retrospective study was performed in Italy (June 2016–June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. Results C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9–3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8–7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9–5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01–0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14–0.55; P < .001) were associated with clinical success. Conclusions Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.

Pseudomonas aeruginosa (PA) is one of the most important causes of healthcare-related infections among Gram-negative bacteria. The best therapeutic approach is controversial, especially for multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains as well as in the setting of most severe patients, such as in the intensive care unit (ICU). Areas covered: This article addresses several points. First, the main microbiological aspects of PA, focusing on its wide array of resistance mechanisms. Second, risk factors and the worse outcome linked to MDR-PA infection. Third, the pharmacological peculiarity of ICU patients, that makes the choice of a proper antimicrobial therapy difficult. Eventually, the current therapeutic options against MDR-PA are reviewed, taking into account the main variables that drive antimicrobial optimization in critically ill patients. Literature search was carried out using Pubmed and Web of Science. Expert commentary: Methodologically rigorous studies are urgently needed to clarify crucial aspects of the treatment against MDR-PA, namely monotherapy versus combination therapy in empiric and targeted settings. In the meanwhile, useful options are represented by newly approved drugs, such as ceftolozane/tazobactam and ceftazidime/avibactam. In critically ill patients, at least as empirical approach, a combination therapy is a prudent choice when a MDR-PA strain is suspected.

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The ultrastructural morphology of the early phases of mycelium-yeast transition in Histoplasma capsulatum after a temperature shift from 25 degrees C to only 34 degrees C is described. Under this condition of lower temperature oxidative phosphorylation is not completely uncoupled and maximum production of heat shock proteins (hsp) occurs. 24 h after temperature shift more than 90% of the cells still appear vital. Alterations in the organization of the mitochondrial cristae are the only ultrastructural changes observed in these cells. In contrast, 70% of the cells degenerate 24 h after a temperature shift from 25 degrees C to 37 degrees C and in the remaining cells mitochondria are rarely observed. These observations are discussed in relation to the production of hsp, the uncoupling of oxidative phosphorylation and the virulence of different strains of H. capsulatum.

Summary: The ultrastructural changes which occur during the first 24 h of mycelium to yeast transition have been studied in the dimorphic fungus Histoplasma capsulatum. A temperature shift controls mycelial to yeast transition. During the first 24 h respiratory rate, ATP and cytochrome concentration fall to very low levels. Ultrastructural observations showed that the plasma membrane became undulated and the cell wall lost its characteristic fibrous outer layer. At 8 h the ordered lammellar structure of the mitochondria was no longer apparent. 24 h after the temperature shift 70% of the cells were lysed. The remaining cells contained many cytoplasmic membrane structures; mitochondria were rarely observed. These changes are considered to be the morphological expression of the physiological events characteristic of stage one in mycelial to yeast transition. Zusammenfassung: Es wurden die Ultrastrukturveränderungen während der ersten 24 h des Myzel‐Hefe‐Phasenwechsels am dimorphen Pilz Histoplasma capsulatum untersucht. Dieser Phasenwechsel wird von einem Temperaturwechsel ausgelöst. Wahrend der ersten 24 h gehen Atmung, ATP und Cytochromkonzentration auf sehr niedrige Werte zurück. Ultrastruktur Untersuchungen zeigen, daß die cytoplasmatische Membran sich stark wellt und die Zellwand ihre charakteristische fibrilläre Aufienschicht verliert. Nach 8h war die geordnete Lamellenstruktur der Mito‐chondrien nicht mehr sichtbar. 24 h nach dem Temperaturwechsel waren 70% der Zellen lysiert. Die verbleibenden Zellen enthielten viele cytoplasmatische Membranstrukturen. Mitochondrien waren nur noch selten zu beobachten. Diese Veränderungen werden als morphologisches Korrelat zu den physiologischen Ereignissen während des Anfangsstadiums des Myzel Hefe‐Phasenwechsels angesehen.