This retrospective multicentre study analysed ICU patients with bloodstream infections (BSI) and/or pneumonia caused by KPC-Kp across five Italian ICUs from January 2021 to December 2023. The primary outcome was 30-day all-cause mortality. Secondary outcomes included early clinical improvement at 72 h, computing the odds ratio (OR) as effect size, and infection-related events. Subgroup analyses were performed based on relevant prognostic factors. The study included 177 patients, with 88 subjects paired after-matching (52 treated with ceftazidime/avibactam [CAZ-AVI] and 36 with meropenem/vaborbactam [MVB]). As for primary outcome, after propensity score matching (PSM), no statistically significant differences in 30-day mortality were observed between the two groups: in the Kaplan-Meier survival log-rank test was p = 0.38, and PSM-adjusted HR of MVB on mortality was 0.65 (95% CI 0.55–1.68). As for secondary outcomes, MVB significantly improved early clinical response post-PSM (OR: 2.19, 95% CI: 1.35–3.55). MVB showed no statistically significant difference in 30-day mortality compared to CAZ-AVI but demonstrated significantly improved in early clinical response for patients with KPC-Kp.

This study investigated the in vitro and in vivo activity of meropenem/vaborbactam (MVB) against two CRKP isolates recovered from catheter-related bloodstream infections in patients undergoing orthopaedic oncologic surgery. Phenotypic assays revealed enhanced biofilm formation and metabolic activity compared to the reference strain Kp ATCC 13883 in the absence of hypervirulence-associated genes. MVB demonstrated bactericidal activity against both planktonic and biofilm-associated cells, with minimum bactericidal concentration (MBC₉₀) and minimum biofilm eradication concentration (MBEC₉₀) values of 0.5/8 μg/ml for CRKP ST101, 0.12/8 μg/ml for CRKP ST307, and 0.25/8 μg/ml for the Kp ATCC 13883 strain. In the Galleria mellonella infection model, MVB significantly improved larval survival following the CRKP challenge. These findings demonstrate that MVB exhibits activity against planktonic and biofilm-associated CRKP cells and highlight the need for further investigation in managing catheter-related bloodstream infections caused by multidrug-resistant K. pneumoniae.

This case series described the use of meropenem/vaborbactam in 2 paediatric patients, ages 11 and 15, with intraabdominal abscesses from CRE. Both patients had clinically improved after the initiation of meropenem/vaborbactam and reported no complications during their follow-up appointments after the completion of their antibiotic courses. These cases demonstrate the safe and effective use of meropenem/vaborbactam in these 2 paediatric patients. Although meropenem/vaborbactam successfully treated both patients’ infections, additional data are needed in this population to determine the safety profile and optimal use for paediatric patients.

This is a case of a 4-year-old girl who developed an intra-abdominal and bloodstream infection caused by a KPC-producing ceftazidime/avibactam-resistant strain of Klebsiella pneumoniae and was successfully treated with a combination of fosfomycin disodium plus meropenem/vaborbactam, optimized by therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA). This clinical case provides evidence that a TDM-guided meropenem/ vaborbactam-optimized regimen could be helpful in the treatment of KPC-Kp intra-abdominal infections in children. Further studies are needed to ascertain the safety, optimal use, and dosage of meropenem/vaborbactam in paediatric patients.

Observational retrospective study objectives to evaluate the effectiveness and safety of cefiderocol (CFDC) in clinical practice in non-critical patients, including all adult patients treated with CFDC between January 2020 and March 2023 in a tertiary hospital. Effectiveness was measured in terms of clinical and microbiological cure seven days after the end of treatment. To assess safety, adverse effects potentially associated with CFDC were collected. A total of 17 patients (80% men) with a median age of 57 years were included. The predominant focus of infection was urinary (47%). The main causal microorganism of the infection was P. aeruginosa (59%). Eleven isolates (65%) were carbapenemase-producing gram-negative bacilli (GNB); the rest (35%) was classified as extensively-drug resistant GNB (XDR-GNB) with other resistance mechanisms. The isolated carbapenemases were one GES, one KPC, eight metallo-beta lactamases (seven VIM type and one NDM), and one carbapenemase without type identification. Treatment with CFDC was completed in all the patients. Fifteen (88%) patients were clinically cured. Regarding microbiological cure, 12 (70%) had negative cultures. CFDC achieves clinical and microbiological improvement in non-critical patients with infections with limited therapeutic options while maintaining a good safety profile.

This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022-2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with ceftazidime-avibactam + aztreonam (CAZ-AVI + ATM); in the second, with double carbapenem therapy (DCT); and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients were independently associated with survival. Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs.

This multicentre, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure-defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy-in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapses or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous population

This study aimed to compare mortality rates and treatment efficacy between ceftazidime–avibactam (CAZ-AVI) and meropenem-based combination regimens in critically ill patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infections. This retrospective study included 135 intensive care unit (ICU) patients diagnosed with CRGNB infections between 2020 and 2024. Among the patients, 74 received CAZ-AVI, whereas 61 were treated with meropenem-based regimens. No significant differences were observed in the baseline characteristics between the groups. There were no statistically significant differences in 14-day (27.0% vs. 31.1%), 30-day (41.9% vs. 47.5%), or 90-day mortality rates (62.2% vs. 65.6%) between the two groups (p = 0.738, 0.511, and 0.818, respectively), including within the pneumonia and bloodstream infection subgroups. Clinical success was observed in 64.9% of the CAZ/AVI group and 65.6% of the other group (p = 0.931), with comparable ICU lengths of stay (44.0 ± 29.1 vs. 41.5 ± 26.4 days, p = 0.974). Multivariate analysis revealed that advanced age, higher Sequential Organ Failure Assessment (SOFA) scores, elevated procalcitonin levels, and prolonged time from culture collection to the initiation of appropriate antibiotic therapy were independent predictors of increased 30-day mortality. CAZ-AVI demonstrated efficacy and mortality outcomes comparable to those of meropenem-based regimens in ICU patients with CRGNB infections. Prompt initiation of appropriate antimicrobial therapy remains critical.

This clinical trial evaluated the non-inferiority of delafloxacin versus the best available therapy (BAT) for the treatment of superficial or deep incisional Surgical Site Infections (SSI) following a cardiothoracic/related leg or abdominal surgical procedure. In this randomized, observer-blinded, active-controlled, parallel-group, multicentre, phase IIIb study, patients with SSI diagnoses were randomized 1:1 to receive delafloxacin 300 mg IV/450 mg OS or BAT IV/OS (vancomycin or linezolid for cardiothoracic SSI, piperacillin/tazobactam or tigecycline for abdominal SSI). A total of 266 patients (delafloxacin=134; BAT=132) with baseline characteristics comparable between the two treatment arms. Delafloxacin clinical success was non-inferior compared with BAT in patients with SSI at TOC visit (91.8% vs. 90.2%, respectively). Similar efficacy was confirmed also at LFU visits (91.8% delafloxacin vs. 87.9% BAT). Delafloxacin demonstrated to be non-inferior in terms of “Cure” response at TOC, as well as at LFU visit. Comparable microbiological response was obtained with delafloxacin and BAT (89.5% and 79.4%, respectively). Delafloxacin and BAT demonstrated comparable treatment adverse event rate (23.9% and 19.7%, respectively), mostly mild to moderate gastrointestinal reactions. DRESS (Delafloxacin intRavenous and oral monothErapy in Surgical Site infections) study provided new data on delafloxacin efficacy in SSIs, covering the need of effective empiric treatment against the wide spectrum of pathogens involved in these difficult to treat infections.

Prompt eradication of Pseudomonas aeruginosa following isolation in sputum samples is a fundamental part of therapy in people with cystic fibrosis in order to prevent chronic infection. Whilst multiple eradication regimens exist, none have been proven to be more efficacious than any other. Eradication treatment is effective but not always successful. Delafloxacin, a fourth-generation fluoroquinolone, has been shown to have superior activity against Pseudomonas aeruginosa compared to ciprofloxacin in-vitro. This case is the successful eradication of Pseudomonas aeruginosa in a person with CF following a new isolation of the pathogen using oral delafloxacin in combination with nebulised tobramycin, instead of ciprofloxacin after the failure of first line treatment and the emergence of ciprofloxacin-resistance on antimicrobial sensitivity testing.

To determine the activity of delafloxacin against invasive S. pneumoniae isolates resistant to levofloxacin (LEV-R), compare delafloxacin MICs for LEV-R isolates with those of susceptible strains, and analyse mutations in QRDRs. A total of 130 S. pneumoniae isolates (2014–20) were studied, thar were distributed according to levofloxacin MICs: high-level LEV-R (n = 46; MIC > 32 mg/L), low-level LEV-R (n = 36; MIC range 3–12 mg/L) and susceptible (LEV-S; n = 48; MIC ≤2 mg/L). The authors considered delafloxacin-resistant to be MIC ≥ 0.12 mg/L (EUCAST epidemiological cut-off). All isolates were subjected to PCR and sequencing of parC, parE, gyrA and gyrB genes. All LEV-S isolates showed delafloxacin MICs of ≤0.008 mg/L and did not show mutations in QRDRs. Isolates with levofloxacin MICs of 3–12 mg/L showed delafloxacin MICs of <0.12 mg/L, with 3 (8.3%) presenting mutations in gyrA, and 11 (30.6%) in parC previously related to resistance. Isolates with levofloxacin MICs of >32 mg/L showed two to four mutations in QRDRs and 11 (24%) were delafloxacin resistant, presenting at least two mutations in gyrAS81F/L/V + parCS79F; four accumulated three mutations, and two showed four mutations in QRDRs. Among LEV-R pneumococci, 71 (87%) were susceptible to delafloxacin, indicating that delafloxacin maintains its activity despite the presence of mutations in gyrA + parC that lead to high-level resistance to levofloxacin.

Levofloxacin and delafloxacin susceptibility of 98 Helicobacter pylori strains in 2020-2023 was examined. Levofloxacin resistance was 33.7%, while delafloxacin resistance was 2.0% at 1 mg/l (the levofloxacin resistance breakpoint for H. pylori), and 9.2% at 0.125 mg/l (the recently suggested delafloxacin ECOFF for the species). Overall proportion of the strains exhibiting >0.125 mg/l delafloxacin MICs was similar to that in a previous study in 2018-2019 (8.5%). None of the 65 levofloxacin susceptible strains had delafloxacin MICs of >0.125 mg/l. Among levofloxacin resistant strains, delafloxacin MICs >1 mg/l (6.1%, 2/33 strains) were detected only in 2022 and 2023. Briefly, the results showed the much higher activity of delafloxacin over levofloxacin. The high delafloxacin activity in acidic environments is an additional advantage of the newer fluoroquinolone for treating H. pylori infection.

Delafloxacin is a potent anionic fluoroquinolone approved for the treatment of respiratory infections that acts by trapping the DNA cleavage complexes of bacterial topoisomerase IV and gyrase. Its N-1-pyridinyl-, C-7-azetidinyl- and C-8-chlorine substituents confer enhanced antibiotic activity against bacteria resistant to other fluoroquinolones, but its mode of action is unclear. This study presents the X-ray crystal structures of a delafloxacin-DNA cleavage complex obtained by co-crystallization with Streptococcus pneumoniae topo IV using a graphene nucleant and solved at 2.0 and 2.4 Å resolution. The results obtained on delafloxacin action suggest that intrinsic target affinity contributes to its activity against quinolone-resistant bacteria.

Periprosthetic joint infections (PJIs) remain among the most challenging complications in orthopaedic surgery, often requiring prolonged antibiotic therapy and complex surgical interventions. Oritavancin (ORI) has emerged as a potential off-label agent in PJI treatment due to its favourable pharmacokinetic properties, potent Gram-positive coverage, and documented antibiofilm activity. This comprehensive review aims to assess the current clinical and preclinical data regarding the potential use of ORI in the management of PJIs. A comprehensive literature search was conducted in three major databases. Six studies were included. In vitro data demonstrated strong activity of ORI against methicillin-resistant S. aureus and S. epidermidis biofilms, particularly in synergy with rifampin. Clinical reports described successful outcomes in both acute and chronic PJI cases, including those with limited surgical options. Weekly or monthly dosing regimens were well-tolerated and effective in suppressive and curative contexts. Adverse events were infrequent but included infusion-related reactions. ORI represents a promising adjunct or alternative to conventional antimicrobial regimens in PJIs, particularly for outpatient management or in patients with multidrug-resistant Gram-positive infections. Further prospective studies are needed to define its role, optimal dosing, and long-term efficacy in this complex clinical setting.

Though current guidelines suggest clear recommendation on initial and eventually alternative treatments on recurrent infective endocarditis (IE) by Enterococcus faecalis, no clear data are currently available on the optimal strategy for patients with recurrent IE by E. faecalis who are not surgical candidates. Oritavancin (ORI), long acting lipoglycopeptide with bactericidal activity against Gram-positive bacteria, including E. faecalis. Though it is approved as a single 1200 mg IV dose for the treatment of acute bacterial skin and skin structure infections (ABSSSIs), due to its favourable pharmacokinetic/pharmacodynamics properties and safety profile, ORI is considered a possible option for beyond-the-label infections such as endocarditis and osteomyelitis that need longer treatments. In this case report, authors explore the innovative use of ORI as long-term antibiotic treatment in a patient with four recurrences of IE due to E. faecalis and who repeatedly refused the surgical procedure.

Oritavancin (ORI) is emerging as a potential alternative to standard antibiotic regimens in the treatment of infective endocarditis caused by gram-positive bacteria, though evidence remains limited. Authors hereby report seven cases of enterococcal endocarditis treated with ORI as consolidation: sequential therapy, for infective endocarditis therapy, resulting in six cures and one relapse. There findings suggest that ORI may offer a safe and effective treatment consolidation strategy, particularly valuable in elderly patients with comorbidities and polypharmacy, in whom prolonged hospitalization and complex antibiotic regimens are often unfeasible. Moreover, these data may help guide future studies to address the current evidence gap on the clinical efficacy of ORI in this setting

The DOTS study was an open-label, assessor-masked, randomized clinical trial conducted to evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteraemia from April 2021 to December 2023 at 23 medical centres in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus bacteraemia who achieved blood culture clearance following at least 72 hours, but no more than 10 days of initial antibacterial therapy were included. Participants were randomly assigned to receive either 2 doses of intravenous dalbavancin (n = 100; 1500 mg on days 1 and 8) or 4 to 8 total weeks of standard intravenous therapy (n = 100; cefazolin or ant staphylococcal penicillin if methicillin susceptible; vancomycin or daptomycin if methicillin resistant. The primary outcome was the desirability of outcome ranking (DOOR) at day 70, which involved 5 components (clinical success, infectious complications, safety complications, mortality, and health-related quality of life) and was assessed for superiority (achieved if the 95% CI for the probability of dalbavancin having a superior DOOR was >50%). Secondary outcomes included clinical efficacy at day 70 (prespecified noninferiority margin of 20%) and safety. Of 200 participants randomized (mean [SD] age, 56 [16.2] years; 62 females [31%]), 167 (84%) survived to day 70 and had an efficacy assessment. The probability of DOOR at 70 days with dalbavancin vs standard therapy was 47.7% (95% CI, 39.8% to 55.7%). Regarding secondary outcomes, clinical efficacy was documented in 73 of 100 for dalbavancin and 72 of 100 for standard therapy (difference, 1.0% [95% CI, -11.5% to 13.5%]), meeting the noninferiority criterion. Serious adverse events were reported in 40 of 100 participants who received dalbavancin and 34 of 100 participants who received standard therapy; treatment-related adverse events were uncommon in both groups. Among adult participants with complicated S aureus bacteraemia who achieved blood culture clearance, dalbavancin was not superior to standard therapy by desirability of outcome ranking.

In this study, the medical records of all patients (n = 66) who received dalbavancin in Region Västmanland, Sweden, from 2019 to 2023 were retrospectively analysed. The primary outcome was clinical cure at 6 months; secondary outcomes included mortality, need for suppressive therapy, and adverse events. Sixty-six patients (median age 73 years; 47% female) received dalbavancin for orthopaedic/bone infections (56%), endocarditis (23%), vascular graft infections (6%), bacteraemia (6%), sacral ulcer infections (6%), and other infections (3%). The patients had significant comorbidities: diabetes (38%), malignancy (33%), chronic kidney disease (44%), and substance use disorders (17%).”Methicillin-susceptible” Staphylococcus aureus was the predominant pathogen (31% of isolates. Patients received a median of 2 doses (range 1-17). At 6-month follow-up, 62% achieved clinical cure, 18% remained on suppressive therapy, and 20% died, primarily from underlying conditions. Adverse events were infrequent (6%) and generally mild. Dalbavancin achieved a 62% cure rate despite significant comorbidities, offering a safe alternative to inpatient care for elderly, comorbid patients.