Background. Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy. Methods. A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)–based dosing approach. Results. Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87–11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9–9.2; P < .001) and age (1.03; 1.0–1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12–.57; P < .001). Conclusions. In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as “rescue” treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug.

Perioperative goal-directed therapy (GDT) reduces the risk of renal injury. However, several questions remain unanswered, such as target, kind of patients and surgery, and role of fluids and inotropes. We therefore update a previous analysis, including all studies published in the meanwhile, to clarify the clinical impact of this strategy on acute kidney injury. Randomized controlled trials enrolling adult patients undergoing major surgery were considered. GDT was defined as perioperative monitoring and manipulation of hemodynamic parameters to reach normal or supranormal values by fluids alone or with inotropes. Trials comparing the effects of GDT and standard hemodynamic therapy were considered. Primary outcome was acute kidney injury, whichever definition was used. Meta-analytic techniques (analysis software RevMan, version 5.3) were used to combine studies, using random-effect odds ratios (OR) and 95% confidence intervals (CI). Trial sequential analyses were performed including all trials and considering only low risk of bias trials. Sixty-five trials with an overall sample of 9308 patients were included. OR for the development of renal injury was 0.64 (95% CI, 0.62–0.87; p = 0.0003), with no statistical heterogeneity. Trial sequential analyses and sensitivity analysis including studies with low risk of bias confirmed the main results. A significant decrease in renal injury rate was observed in studies that adopted cardiac output and oxygen delivery as hemodynamic target and that used both fluids and inotropes. The postoperative kidney injury rate was significantly lower in trials enrolling “high-risk” patients and major abdominal and orthopedic surgery. The present meta-analysis suggests that targeting GDT to perioperative systemic oxygen delivery, by means of fluids and inotropes, can be the best way to improve renal perfusion and oxygenation in high-risk patients undergoing major abdominal and orthopedic surgery.

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64–78) vs. 62 (IQR 52–69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6–8) vs. 4 (IQR 2–6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9–11) vs. 9 (IQR 7–11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04–1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19–0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17–0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.

Despite preventive measures, ventilator-associated pneumonia (VAP) remains the most common healthcare-associated infection in the intensive care unit (ICU). VAP's striking incidence and impact are a leading cause of morbidity and prolonged ICU stay. This study focused on the characteristics and outcomes of patients diagnosed with ICU-acquired VAPs in Italian ICUs. Data were drawn from the PROSAFE network, a prospective multicentric observational project conducted across 192 Italian ICUs (2014-2023). Clinical data were recorded following the European Centre for Disease Prevention and Control VAP definitions. The incidence rate was estimated, and multivariable logistic regression identified ICU mortality risk factors. The patients admitted to the included ICUs were 402 085. Among 122 430 classified at risk for VAP because of invasive mechanical ventilation (IMV) ≥48 hours, a total of 11 978 VAP cases were identified, corresponding to a prevalence of 9.8%. The incidence rate of VAP was 10.47 cases per 1 000 ventilator days (95% CI: 10.28-10.66). Patients with VAP exhibited prolonged ICU stays (median: 23 days, Q1-Q3: 15-36) and high mortality (30.0%). Microbiological profiling of VAP identified Pseudomonas spp. (21.0%), Staphylococcus aureus (20.2%), and Klebsiella spp. (20.1%) as the predominant pathogens. The logistic regression showed that older age, chronic liver and kidney diseases, multidrug-resistant organisms, and Acinetobacter spp. aetiology and duration of ICU stay before VAP were significantly associated with higher mortality. While confirming the overall high mortality of patients undergoing IMV, our findings highlight the significantly prolonged ICU stay in VAP patients, and the influence of multidrug-resistant organisms on VAP-related mortality. These insights emphasize the necessity for effective and timely preventive strategies, as well as the early identification of VAP aetiology.

Serratia marcescens (SM) is a Gram-negative bacterium that is frequently found in the environment. Since 1913, when its pathogenicity was first demonstrated, the number of infections caused by SM has increased. There is ample evidence that SM causes nosocomial infections in immunocompromised or critically ill patients admitted to the intensive care units (ICUs), but also in newborns admitted to neonatal ICUs (NICUs). In this study, we evaluated the possible genetic correlation by PFGE between clinical and environmental SM strains from NICU and ICU and compared the genetic profile of clinical strains with strains isolated from patients admitted to other wards of the same hospital. We found distinct clonally related groups of SM strains circulating among different wards of a large university hospital. In particular, the clonal relationship between clinical and environmental strains in NICU and ICU 1 was highlighted. The identification of clonal relationships between clinical and environmental strains in the wards allowed identification of the epidemic and rapid implementation of adequate measures to stop the spread of SM.