This study aimed to evaluate the effectiveness and safety of Meropenem-vaborbactam for treating carbapenem-resistant Enterobacterales (CRE) infections based on real-world data.Real-world evidence from registries and non-selected case series involving 10 or more adult patients treated with Meropenem-vaborbactam for CRE infections was included. Meta-analyses using a random-effects model were performed, with the primary outcomes being clinical efficacy and survival, including 30-day and 90-day survival rates. Out of 1862 potentially relevant publications, six studies were included in the meta-analysis. The pooled clinical success rate was 75% (95% CI, 66%-82%), and the pooled 30-day and 90-day survival rates were 75% (95% CI, 71%-78%) and 69% (95% CI, 61%-76%), respectively. Importantly, no serious adverse effects were reported. In conclusion, Meropenem-vaborbactam demonstrated both efficacy and safety in treating CRE infections in real-world settings.

Among drug-resistant bacteria, carbapenem-resistant Enterobacterales (CRE) are a major clinical challenge with limited options for treatment. In the last several years, new treatment options have emerged for CRE, including meropenem–vaborbactam (MVB). MVB was studied clinically in the TANGO-I and TANGO-II trials, which evaluated the combination in complicated urinary tract infections and in different types of CRE infections, respectively. To date, clinical data on the efficacy of MVB in treatment of CRE remain limited but are needed to understand the efficacy of a drug in routine practice. Eight retrospective studies have investigated the use of MVB for CRE. In these analyses, the overall clinical success rate varied from 60 to 75%, while mortality rates at 30 days ranged from about 15 to 30%. Most of these investigations involved patients with KPC-producing CRE strains, but also patients with Gram-negative infections, of which 80% were CRE. In addition, a number of small case series and case reports have emerged describing the use of MVB. In both retrospective studies and case series/reports, there appeared to be no major safety concerns. Collectively, these data have shown that MVB can be considered to have promising efficacy in severe Klebsiella pneumoniae carbapenemase (KPC)-producing-CRE infections and is safe and well tolerated.

Infective ventriculitis can arise after neurosurgical procedures, with a mortality rate of 15-23%. Cases involving multidrug-resistant Gram-negative bacteria (MDR-GNB), particularly Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp), are increasing. Case 1 involved a 41-year-old man with a ruptured arteriovenous malformation managed with an external ventricular drain (EVD). Forty-eight hours later, he developed a fever, and CSF samples confirmed KPC-Kp infection. Initial therapy with ceftazidime-avibactam was switched to (MVB) administered as an extended 8-hour infusion plus fosfomycin. After 14 days of treatment, microbiological eradication was achieved, but the patient later died from cerebrovascular complications.

Case 2 was a 64-year-old woman who, after a decompressive craniotomy for ischemic stroke, developed a wound infection from ESBL-producing K. pneumoniae. Chemical examination of cerebrospinal fluid (CSF) was suggestive of ventriculitis, and cultural examination was positive for K. pneumoniae, which showed resistance to meropenem, and treatment was adjusted to MVB with intravenous ciprofloxacin. Six weeks of MVB and four weeks of ciprofloxacin, MRI showed lesion reduction, and therapy was stopped. Although data on MVB’s therapeutic drug monitoring (TDM) is limited, these cases demonstrate MVB’s potential efficacy as part of an IV combination therapy for shunt-related ventriculitis, suggesting that extended infusion could serve as an intrathecal-sparing approach in select cases.

A 60-year-old man with a ventriculoperitoneal shunt for encephalocele was admitted to the hospital for fever and altered mental status. Blood cultures revealed KPC-producing Klebsiella pneumoniae, and treatment with ceftazidime-avibactam and tigecycline was started. Due to suboptimal response, meropenem-vaborbactam replaced initial therapy, and meropenem and vaborbactam levels were determined in both blood and CSF samples. Steady state meropenem concentrations were 44.5 mg/L in blood and 10.1 mg/L in CSF, respectively; steady state vaborbactam concentrations were 51.3 mg/L in blood and 40.9 mg/L in CSF, respectively, with a cerebrospinal fluid/plasma ratio of approximately 80%. The patient improved clinically and completed a 6-week antibiotic course before discharge.

This study investigated MVB activity against planktonic and biofilm forms of 24 CRKP (carbapenem-resistant Klebsiella pneumoniae) isolates, including 22 KPC and 2 VIM-producing strains. The whole genome sequencing (WGS) analysis identified four distinct sequence types (ST307, ST512, ST101, and ST66. All isolates were susceptible to MVB. The median MIC90 for planktonic isolates was 0.25 μg/mL (range: 0.03–4.0 μg/mL). Similarly, the median MBEC90 for biofilm-associated isolates was 0.25 μg/mL (range: 0.06–32 μg/mL). MVB was effective against VIM-producing strains in planktonic form, but these strains showed reduced susceptibility in biofilm, correlating with higher biomass production. MVB demonstrated high efficacy against both planktonic and biofilm forms of KPC-producing CRKP isolates.

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 hours from therapy start and infection-related events. Among 177 patients included (123 CZA, 54 MVB), the matched cohort was made of 88 subjects (52 CZA, 36 MVB). Pre-matching, 30-day mortality was lower in patients with septic shock (SS) treated with MVB (HR: 0.47, 95%CI: 0.22–0.99), but post-matching, the difference was not statistically significant (HR: 0.39, 95%CI: 0.10–1.56). In patients on MVB, MVB showed a trend toward lower mortality post-matching (HR: 0.44, 95% CI: 0.15–1.28). MVB was associated with significantly higher odds of early clinical improvement post-matching (OR: 2.19, 95% CI: 1.35–3.55). Early improvement rates were 61.1% for MVB versus 36.5% for CZA (p=0.01). MVB showed no statistically significant difference in 30-day mortality compared to CZA but demonstrated significantly improved early clinical outcomes in patients with KPC-Kp infections.

A sum of 214 non-duplicate strains of KPC producing K. pneumoniae were isolated from clinical specimens (90 from urine, 59 from blood, 36 from pus or tissue, 24 from respiratory and 5 from body fluids. Strains out of 214 (0,46%) was resistant to ceftazidime/avibactam. No resistant strains to imipenem/relebactam or meropenem/vaborbactam were found. Ceftazidime/avibactam had MIC50/MIC90= 1.0/2.0 μg/ml, imipenem/relebactam had MIC50/MIC90= 0.25/0.50 μg/ml and meropenem/vaborbactam had MIC50/MIC90= 0.50/1.0 μg/ml.

This abstract describes a case of sternal osteomyelitis caused by KPC-producing Klebsiella pneumoniae (Kp-KPC) in a recent lung transplant (LuTx) recipient. A 44-year-old patient underwent bilateral LuTx due to graft-versus-host disease following allogeneic haemopoietic stem cell transplantation. The patient was extubated on day 1. On day 3, broncho-aspirate revealed airway colonization by K. pneumoniae KPC+ sensitive to MVB, imipenem/relebactam, aminoglycosides, and colistin but resistant to ceftazidime/avibactam and ceftolozane/tazobactam. On day 20, septic pneumonia due to Kp-KPC occurred: the patient was treated with meropenem/vaborbactam (2/2g every 6 hours via 3 hours extended infusion for 10 days), leading to resolution and hospital discharge. Forty days post-transplant, the patient, afebrile, underwent chest CT for persistent parasternal pain, revealing surgical wound dehiscence and retrosternal fluid. Intraoperative samples revealed presence of Kp-KPC showing the same susceptibility pattern as the previous strain. The patient was started on MVB (2/2g every 6 hours via 3 hours extended infusion) and continued therapy for 8 weeks. A follow-up CT scan after 10 weeks showed complete resolution of the infection. Ten months after discontinuation of therapy, the patient remained asymptomatic. MVB was the drug of choice due to the Kp-KPC strain’s susceptibility pattern, indeed its effectiveness in lung distribution and favourable PK/PD profile made it suitable for non-standard and prolonged use in treating sternal osteomyelitis post-LuTx

A multicentric retrospective cohort study was conducted on patients treated with CZA or MVB for microbiologically documented KPC-producing K. pneumoniae infections between 2018 and 2024, enrolled in the SUSANA (Surveillance of Safety and Outcome of New Antibiotics) cohort. One-hundred thirty patients were enrolled (104 in CZA, 26 in MVB). The most represented site of infection was the lower respiratory tract (36.5% in the CZA group and 34.6% in the MVB group). Concomitant bacteraemia was present in 61(58.7%) patients in the CZA group and in 16(61.5%) patients in the MVB. The evaluated outcomes yielded comparable results between the two groups: clinical cure was achieved in 65(62.5%) patients in the CZA group vs 17(65.4%) in the MER/VAB, in-hospital mortality was 25(24.0%) vs 7(26.9%) and recurrence was 14(10.8%) vs 2(7.7%), respectively(p-value=0.719). Kaplan-Meier survival curves showed no significant difference in overall 28-day survival (22.1% vs 26.9%, log-rank p=0.621) between the two groups although intensive care unit admission represented a risk factor for 28-day mortality(p=0.0141). Adverse events were rare in both cohorts: among the CZA group 6 events (4.62%) were reported, which included neuralgia, platelet count decrease, urticaria vs 1(0.77%) in the MVB group (pancytopenia). CZA and MVB are effective treatments for KPC K. pneumoniae infections, showing similar clinical outcomes.

In England, a pilot project with a prepaid subscription model to incentivize antibiotic development began in December 2020, selecting ceftazidime/avibactam as one of the pilot antibiotics. For future evaluation of this model, the authors wanted to estimate levels of ceftazidime/avibactam use, susceptibility testing, and resistance before the start of the pilot. Since resistance can be conferred by some carbapenemases, carbapenemase genes have been studied in some resistant bacteria. The authors learned that levels of ceftazidime/avibactam use, and susceptibility testing appear to have increased in the period before the pilot. Additionally, low levels of resistance have been observed in the country, in some cases coinciding with the presence of some carbapenemase genes in bacteria. There was also suspicion of resistance development in one patient during treatment with ceftazidime/avibactam. This analysis highlights the importance of identifying the carbapenemase gene prior to the use of ceftazidime/avibactam. There is also a potential risk of developing resistance during treatment. Best practice is to establish individual treatment plans for individual patients using microbiology and surveillance data; it is also important that microbiologists and clinicians identify and report emerging resistance to ceftazidime/avibactam in bacteria to prevent its spread.

To evaluate the susceptibility profiles of regional inpatient meropenem-resistant (MEM-R) carbapenemase-producing Enterobacterales (CPE) isolates and their MIC values to ceftazidime-avibactam (CZA), meropenem-vaborbactam (MVB), and aztreonam-avibactam (ATM-AVI), authors analysed 2020-2022 data from the Antimicrobial Testing Leadership and Surveillance. Carbapenemase-encoding genes in CPE isolates were identified using multiplex PCR and Sanger sequencing. Susceptibility breakpoints for CZA and MVB recommended by CLSI 2024 and EUCAST 2025 against Enterobacterales were applied. A total of 2,318 CPE isolates (78.2% were K. pneumoniae) were tested globally. Notable diversity in carbapenemase-encoding gene distributions was observed among CPE isolates from Africa/the Middle East (10 countries; n=361), Asia (7 countries, excluding India and Pakistan; n=182), Europe (17 countries; n=1,002), and Latin America (10 countries; n=773). Metallo-β-lactamase-encoding genes, predominantly blaNDM-1, were more frequently detected in CPE isolates from Africa/the Middle East and Asia compared to other regions. Among KPC variants, the KPC-2 enzyme was the predominant one in CPE isolates in Europe and in Latin America. The susceptibility rates of all analysed CPE isolates harbouring only a single blaKPC gene to CZA and MVB were 99.4% and 93.5%, respectively, based on the CLSI 2024 susceptibility breakpoints. The MIC50/90 values of CPE isolates to ATM-AVI were 0.12/0.25 mg/L and 0.5/1 mg/L, respectively, regardless of collection region, dual carbapenemase production, or infection source. These trends in resistance to novel antibiotics among contemporary CPE isolates need close monitoring.

To address this knowledge gap, a multicenter real-world study was conducted. CRPA-infected patients treated with PMB (Polymyxin B) or Ceftazidime/avibactam (CZA)-based regimens were enrolled from five hospitals between Jan 1, 2021, to July 31, 2023. # 170 Carbapenem-resistant Pseudomonas aeruginosa (CRPA)-infected patients were enrolled, among whom 124 (72.9%) had difficult-to-treat resistant P. aeruginosa (DTR-PA) infections and 77 (45.3%) received CZA-based regimens. The occurrence of Acute Renal Injury (AKI) in patients with CRPA infection was associated with underlying diseases, including sepsis/septic shock, and diabetes mellitus. In addition, other CREs infection, APACHE II score were found to be independent predictors of 30-day all-cause mortality. In conclusion, CZA-based regimens demonstrated superior efficacy in clearing CRPA compared to PMB-based regimens. Furthermore, several factors associated with AKI and mortality in CRPA-infected patients were identified, highlighting the need for further research to optimize treatment strategies.

This is a multicentre, retrospective cohort study conducted in the period between 2017 and 2023 at five institutions for patients who received either CZA or colistin-based regimens for treating MDR P. aeruginosa infections. Outcomes were compared using multivariate logistic regression analysis. Among the screened patients, 203 patients were included: 89 in the CZA group and 114 in the colistin group. A total of 57% presented with pneumonia, 21% with bacteraemia, and 61% were in the intensive care unit. The rate of clinical cure was significantly higher among patients who received CZA (67% vs. 50%). The rate of in-hospital mortality was numerically lower among patients who received CZA (40% vs. 49%). The rate of AKI was significantly lower among patients who received CZA (15% vs. 43%). CZA was more effective in treating MDR P. aeruginosa infections and showed a better safety profile compared to colistin. Thus, CZA could be a better alternative for treating MDR P. aeruginosa infections.

This is a multicenter survey analysing data from the SUSANA cohort. The aim was to evaluate the efficacy of the newer antibiotics, and to compare clinical outcomes in patients with nosocomial pneumonia caused by P. aeruginosa treated with either CTZ or CZA. Primary endpoint was 28-day mortality from treatment start. Overall, 115 patients were included. Of them, 72.2% received CTZ and 27.8% CZA. There was no statistically significant difference between the two groups in terms of age, sex, chronic kidney disease, immune-depression, septic shock, ICU admission, VAP, and prolonged or continuous antibiotic’s infusion. However, patients treated with CTZ were more often affected by chronic obstructive pulmonary disease (p=0.03), while in the CZA group patient were more frequently treated with a combination with IV fosfomycin (p<0.0001).The 28-day mortality rate was similar between the two groups (24.1% for CTZ vs. 21.9% for CZA, p=0.81). CTZ and CZA offer a comparable efficacy in terms of 28-day survival rates for nosocomial pneumonia caused by P. aeruginosa.

Eleven CRKP strains causing disease (D) or colonization (C) in a lung transplant recipient over ~4 years underwent Illumina whole genome sequencing. Antibiotic-resistance evolved in mutHV76G strains: C5, D4 and C6 were meropenem-susceptible, ceftazidime-avibactam-resistant KPC-46-carriers (KPC-3-D179Y); D5 was a meropenem-resistant, ceftazidime-avibactam-resistant KPC-61-carrier (KPC-3-S171P). Hypermutator CRKP emerged due to mutHV76G, which conferred increased propensity to SNPs, transference and acceptance of antibiotic-resistance-conferring plasmids, heightened virulence, and β-lactam/β-lactamase resistance in vitro and in vivo.

This study evaluates clinical and microbiological features, microbiological profiles, and outcomes, focusing on resistance patterns, antibiotic therapy, and mortality. This was a retrospective study of hospitalized patients treated with ceftazidime–avibactam (alone or with aztreonam) for ≥72 hours between November 1, 2019, and September 30, 2024. A total of 109 patients were included (62% male, median age 49 years, range 16–88), with a median hospital stay of 31 days (range 4–248). Severe clinical scores were noted in 19% (PITT score ≥4), 32% (CCI ≥4), and 38% (INCREMENT score ≥8). All patients received empiric therapy (median duration 3 days), most commonly ceftazidime-avibactam with aztreonam (39%). Targeted therapy was administered to 77% (median duration 7 days), often with the ceftazidime-avibactam with aztreonam (48%). Despite clinical cure was achieved in 74%, overall mortality reached 33%, with 16% attributed to infection. ICU admission (p=0.034, OR 4.1), INCREMENT score ≥8 (p=0.035, OR 3.5), and urinary catheter use (p=0.025, OR 4.6) were independently linked  to higher mortality. Ceftazidime–avibactam, particularly with aztreonam, is effective against MDR pathogens, including MBL-resistant strains. ICU admission, high INCREMENT scores, and urinary catheter use are Link ed to higher mortality, stressing the need for vigilant risk assessment and tailored therapy.

To investigate the epidemiology and resistance profile of CR-Kp from Greek ICUs, CR-Kp isolates were consecutively collected between May 2021 and December 2024 from 17 ICUs as part of the prospective, non-interventional, nationwide INCREASE cohort study. A total of 271 CR-Kp were included, of which 257 were successfully sequenced. Most CR-Kp were isolated in blood (69%) and respiratory samples (20.3%). All isolates (271/271) were carbapenemase producers, including KPC (48.7%), NDM (21.4%), KPC & NDM (14.4%), KPC & VIM (10.7%) and VIM (4.8%) enzymes. Across all isolates, aztreonam-avibactam exhibited the most potent activity (94.5% susceptibility), followed by cefepime-zidebactam (91.1%) and cefepime-taniborbactam (78.6%). Lower susceptibility rates were noted for cefiderocol (58.3%), tigecycline (53.9%) and colistin (53.5%). These results suggest a multi-clonal spread and increasing prevalence of metallo-β-lactamase-producing and dual-carbapanemase-producing CR-Kp, posing a significant health threat for patients hospitalized in Greek ICUs.

The objective of this study was to analyse the distribution of microorganisms causing BSI and its antibiotics resistance patterns. The study includes a total of 1786 patients with hematologic diseases followed up between September 2023- October 2024. Seventy bacteraemia episodes were identified in 70 patients. Extended-spectrum β-lactamase, quinolone, ceftazidime-avibactam, and amikacin resistance rates in Gram-negative enteric bacilli (GNEBs) were 77%, 83%, 20% and 30%, respectively. Carbapenem resistance was 44% in GNEBs.

This study explores the effects of early versus late administration of CZA in patients with lower respiratory tract infections. This was a multi-centre, retrospective cohort study of adult patients diagnosed with lower respiratory tract infections receiving CZA for ≥72 hours from 2019 –2024. Overall, 296 patients were included (≤48 hours n=84, >48 hours n=212). Late CZA was associated with higher 30-day all-cause mortality (30.7%) than early (15.5%), p-value = 0.008. Clinical success was numerically higher in the early CZA administration group; however, it was not statistically significant (69.0% vs 58.0%, p-value= 0.079). CZA administration within 48 hours of the index culture was significantly associated with lower 30-day all-cause mortality in hospitalized adult patients with lower respiratory infections.

This study quantified the value of ATM-AVI for treating metallo-beta-lactamase (MBL)-producing Enterobacterales HAP/VAP and cIAI, from the Spanish National Healthcare System perspective, considering transmission and diversity value from the STEDI (spectrum, transmission, enablement, diversity, and insurance) framework. Over ten years, an estimated 17,383 MBL-Enterobacterales infections were treated under current practice; with the introduction of ATM/AVI, 732 infections were avoided. ATM-AVI is estimated to prevent 1,733 deaths, and gain 25,696 QALYs, and reduced costs by €45.2 million. The introduction of ATM-AVI was found to be both more effective and less costly for the Spanish healthcare system, translating into a NMB of €687 million. The addition of ATM/AVI for the treatment of MBL-Enterobacterales HAP/VAP and cIAI, in Spain, addresses a clinically significant unmet need and provides significant benefits to the healthcare system resulting in cost savings and improved patient health.

A multicentric, retrospective cohort real-world study was conducted on patients treated with CZA+ATM or CFD for microbiologically documented MBLs infections between 2021 and 2024, enrolled in the SUSANA (Surveillance of Safety and Outcome of New Antibiotics) cohort. Forty-one patients were included (20 treated with CZA+ATM, 21 with CFD). Clinical success was achieved in 85% of CZA+ATM patients vs. 71.4% of CFD patients, while 28-day mortality occurred in 10% and 23.8% of patients, respectively (p=0.499). CZA and CFD appear equally effective treatments for MBL infections, mainly NDM, demonstrating similar clinical outcomes, though the groups are heterogeneous in terms of infectious syndromes

This was a multicenter, retrospective, observational analysis of 23 paediatric patients (median [IQR] age: 4.1 [1.9-12.8] years; weight: 14.1 [10.1-44.2] kg). who received CZA between February 2015 and November 2023. The primary outcome was composite clinical success: lack of 30-day all-cause mortality, lack of 30-day microbiologic and clinical recurrence, and resolution of symptoms of infection while on CZA, without therapy modification due to concerns for failure Most commonly isolated organisms were carbapenem-resistant Enterobacterales (52.2%) and carbapenem-resistant Pseudomonas aeruginosa (30.4%). The CZA regimen used most frequently included 50 mg ceftazidime/kg/dose q8h (34.8%) for a median [IQR] duration of 14.0 [6.8-21.7] days. The primary outcome occurred in 69.6% of patients, while no patients experienced adverse effects. CZA exhibited high clinical success and low adverse effect rates in this paediatric cohort.

In this study the in-vitro susceptibility of clinical K. pneumoniae isolates, collected in 2017-2024, were evaluated 150 K. pneumoniae were selected including 44 MDR non-CRKp, 63 CRKp, and 43 susceptible and preselected putative-hypervirulent K. pneumoniae (hvKp) isolates against recent last-line substances. All isolates were susceptible to aztreonam-avibactam. In total, 30 (20%) isolates showed resistance to ceftazidime-avibactam. Carbapenemase-production was detected in 74.6% of CRKp, including: NDM, OXA, KPC and VIM. Phenotypic susceptibility testing for aztreonam-avibactam, ceftazidime-avibactam and cefiderocol showed that all isolates were susceptible to aztreonam-avibactam, regardless of the presence of carbapenemases or hypervirulence-associated genes. The proportion of multidrug-resistant isolates carrying hvKp-associated genes was unexpectedly high and emerged since 2022.

This study evaluates the comparative effectiveness of ceftazidime-avibactam versus colistin-based therapies in treating infections caused by XDR gram-negative microorganisms among ICU patients. The study included 191 adult ICU patients diagnosed with infections caused by XDR pathogens and treated with either ceftazidime-avibactam or colistin monotherapy/combination therapy between January 2022 – January 2024. Primary outcomes assessed were clinical, microbiological, and laboratory responses, alongside 28-day and 90-day mortality rates. Klebsiella pneumoniae was the causative microorganism for 95.8% of the infections. The adjusted multivariate logistic regression analysis revealed no statistically significant differences in the primary outcomes of 28-day and 90-day mortality (p values of 0.440 and 0.824, respectively) between ceftazidime-avibactam and colistin monotherapy/combination groups. However, nephrotoxicity was significantly higher in patients treated with colistin-based therapies, occurring at a rate 5.6 times greater than in those treated with ceftazidime-avibactam (p<0.001, 95% CI: 2.213-14.257). Ceftazidime-avibactam exhibits comparable efficacy to colistin-based regimens in treating XDR gram-negative bacterial infections in ICU settings, with a more favourable renal safety profile.

This study aimed to compare treatment outcomes between CZA and best alternative therapy (BAT) in CRE bacteraemia. This retrospective cohort study included 353 patients with CRE bacteraemia treated at a tertiary hospital between January 2022 and July 2024. 32 (9.1%) patients received CZA, and 321 (90.9%) patients received BAT for CRE bacteraemia. After propensity score matching, the 14-day mortality rate was significantly lower in the CZA group than in the BAT group (12.5% vs. 35.9%; P=0.030). addition, microbiological clearance was more frequent in the CZA group compared to the BAT group (90.6% vs. 68.8%; P=0.035). Multivariable analysis identified that the use of CZA was independently associated with improved 14-day mortality (adjusted odds ratio, 0.25; 95% confidence interval, 0.07–0.72; P=0.019). The use of CZA was associated with improved survival in CRE bacteraemia.

This study aimed to describe the phenotypic and genotypic characteristics of the KPC-Kp strain resistant to CZA, M/V and CFD. All the 5 isolates belonged to ST512. Four of the five isolates had carbapenem resistance and susceptibility to CZA, CFD and M/V. Patient #1 was treated for 24 days with CZA and, after one month, a second isolate was isolated with resistance to the three antimicrobials. Comparative genome analysis revealed that all 5 strains had the same plasmid and resistance gene context, with the exception of the KPC variant in patient #1. All 4 CZA, CFD and M/V-susceptible isolated produced KPC-3, unlike the resistant isolate, which produced KPC-31 due to an aminoacidic change in the KPC-3 sequence (Asp178Tyr). This work demonstrates an acquisition of resistance in vivo probably related to antibiotic pressure after treatment with CZA.

32 CZA-resistant strains, including 12 CRPA and 20 CRKP strains were obtained from an intensive care unit of a tertiary hospital in China from August 2020 to February 2021. NDM led to CRKP strains CZA resistance and efflux pump, blaAFM-2, blaKPC-87, and blaPER-1 contributed to CZA resistance of CRPA. Compared to KPC-2, KPC-87 exhibited a 1.5-fold elevation in kcat/Km for ceftazidime, a 7.5-fold increase in Ki for avibactam, and a loss of carbapenem hydrolysis. In CRKP and CRPA, especially CRPA, diverse resistance mechanisms contributed to CZA resistance. These CZA-resistant strains were transmitted among patients in the ICU and even across regions to the other healthcare unit when the patient was transferred.

This review evaluated the in vitro efficacy of ceftazidime/avibactam in combination with other antimicrobials against CR-GNB. PubMed, Web of Science, Embase, and Scopus were searched. Study outcomes were quantified by counting the number of isolates exhibiting synergy, defined as a FICI ≤ 0.5 for checkerboard and Etest and a >2 log cfu/mL reduction for time-kill studies. Forty-five in vitro studies were included. A total of 734 isolates were tested, and 69.3% of them were resistant to ceftazidime/avibactam. The combination of ceftazidime/avibactam with aztreonam showed a high synergy rate against carbapenem-resistant Klebsiella pneumoniae (effect size, ES=0.91-0.98) and Escherichia coli (ES=0.75-1.00), however, not against P. aeruginosa. Ceftazidime/avibactam also demonstrated a high synergy rate (ES = 1) in time-kill studies when combined with azithromycin, fosfomycin, and gentamicin against K. pneumoniae. Compared to ceftazidime/avibactam alone, a higher bactericidal rate was reported when ceftazidime/avibactam was combined with other antimicrobials against carbapenem-resistant K. pneumoniae (57% versus 31%) and E. coli (93% versus 0%). Ceftazidime/avibactam frequently demonstrates synergistic bactericidal activity when combined with various antimicrobials against CR-GNB in in vitro tests.

This study evaluated the in vitro effectiveness of these antibiotics against clinical MBL-producing Gram-negative isolates. 256 Non-duplicate MBL-producing Gram-negative isolates with reduced carbapenem susceptibility were collected (2022–2024). Enterobacterales isolates with NDM/OXA-48, NDM, and VIM carbapenemases showed susceptibilities to ceftazidime-avibactam plus aztreonam of 95%, 100%, and 100%, respectively, compared to cefiderocol (46%, 50%, and 58.3%; p < 0.0001). For VIM-producing Pseudomonas spp., cefiderocol susceptibility was 95%, outperforming ceftazidime-avibactam plus aztreonam (80%; p = 0.0042). Cefiderocol demonstrated superior activity against MBL-producing Pseudomonas spp., while ceftazidime-avibactam plus aztreonam was more effective for MBL-producing Enterobacterales.

This was conducted a retrospective multicenter observational study in 22 French centres. From January 2019 to December 2023, 45 patients were included. The vast majority of patients received 6g of CFD per days. CFD was administered in combination in 40 cases out of 45 (89%) with other antibiotics to (i) cover micro-organisms out of the spectrum of CFD (21/45, 47%) and/or (ii) potentiate the antibacterial activity against GNB (31/45, 69%).The median duration of CFD treatment was 34 days. Seven patients (16%) experienced side effects, mainly gastro-intestinal disorders, including 3 (7%) which required treatment withdrawal. Infection control included surgery in 37 (82%) patients. Failures and deaths occurred in respectively, 22 (49%) and 10 (22%) cases. This is the first multicentric cohort study on cefiderocol involving BJIs. These results suggest that CFD may be an alternative in MDR-GNB infections with limited therapeutical options.

Data were extracted from the SUSANA (Surveillance of Safety and outcome of New Antibiotics) database, a retrospective, multicentric cohort study started in November 2019 on the use of new antibiotics for patients with suspected or microbiologically documented MDR infections. This study aimed to assess the impact of cefiderocol therapy on 28-day survival and clinical outcomes in patients with MDR-GNB infections. Ninety-four patients treated with CFD were included; 69 patients (73%) were men, with a median age of 68 years (IQR 57-75). The most common site of infection was the lower respiratory tract (41, 44%). Forty-two patients (45%) developed bacteraemia, 66 (70%) sepsis and 13 (14%) septic shock. The overall clinical cure rate was 65% (61/94) but only 51% (39/51) in patients with CRAB infections. No significant differences in 28-day survival were found between monotherapy and combination therapy (χ2 0.9, p 0.33) or across different MDR infections (χ2 2.9, p 0.39). However, monotherapy carried a significantly higher risk of infection recurrence compared to combination therapy (χ2 3.87, p 0.04). These findings confirm that CFD is effective for the treatment of MDR-GNB. No significant 28-day survival differences between monotherapy and combination therapy or among different pathogens were observed, but a higher risk of infection recurrence was associated with monotherapy.

PROVE was an international, retrospective, observational medical chart review study conducted between November 2020 and July 2024. The PROVE study enrolled a total of 567 patients from five European countries with serious Gram-negative bacterial infections and treated with cefiderocol for ≥72 hours. The clinical outcomes in this European subset of patients were assessed. When cefiderocol was initiated, 55.9% of patients were in the intensive care unit, and 41.3% were receiving organ support. Cefiderocol was prescribed for a documented (prior to initiation) Gram-negative infection in 68.8% of patients. Overall clinical cure rate was 65.3%, and 30-day ACM rate was 25.7%. Among patients with RTIs, clinical cure and 30-day ACM rates were 59.2% and 32.4%, respectively. Similar clinical cure rates were observed among patients with bloodstream infection (60.7%), skin and skin structure infection (63.9%), and intra-abdominal infection (64.7%). Cefiderocol treatment was effective in European patients with confirmed Gram-negative bacterial infections.

This study was a retrospective analysis of 80 adult patients treated with cefiderocol ≥ 72 hours in referral university hospital. The median duration of cefiderocol treatment was 9.50 days (IQR: 5.25 – 20.5) and in 21.2% of cases cefiderocol was combined with other antibiotic, being aerosolized colistin the most frequent option (11.2%). Clinical success was achieved in 67.5% of patients. Overall, 30-day and 90-day case-fatality rates were 27.5% and 36.5%, respectively. Four (5%) patients had recurrence, and resistance emergence was documented only in one NMD-OXA-48-BLEE Klebsiella pneumoniae strain (ST147 clone). Serious adverse effects occurred in 4 patients leading to discontinuation of cefiderocol treatment: rash, dizziness, myoclonic movements, and thrombocytopenia. Cefiderocol demonstrates promising efficacy and safety in managing multidrug-resistant Gram-negative infections, providing a valuable option for patients with limited options.

A retrospective analysis was conducted on cefiderocol use for empirical or targeted treatment of patients with suspected or confirmed severe CR-GNB infections and/or limited therapeutic alternatives at a Spanish tertiary hospital from 2021 to 2024. Data were collected for 33 patients across 36 treatment episodes. Clinical and microbiological cure, excluding cases of colonization/infections without CR-GNB isolation, was achieved in 78% (18/23) and 69% (11/16) of episodes with available results, respectively. The all-cause 28-day mortality rate was 27% (7/26). Cefiderocol demonstrates significant potential for treating CR-GNB infections.

This multicenter study was conducted on 28 selected MDR Gram-negative bacilli strains isolated from clinical samples of the following species: Pseudomonas aeruginosa (n=5), Acinetobacter baumannii (n=11), and Klebsiella pneumoniae (n=12). Overall, CFD MIC50 and MBIC50 was 0.5 mg/L and 64 mg/L, respectively. According to species, we observed the following mean (SD) fold increase of CFD susceptibility between planktonic and sessile cells for P. aeruginosa, A. baumannii and K. pneumoniae: 9.60 (0.55), 6.27 (2.28), and 6.25 (2.80), respectively. When 8 mg/ml CFD was tested against all strains, we observed that the best median (IQR) percentage reduction results were obtained in cfu counts and extracellular matrix percentage of occupation area (67.8 [47.7-80.2] and 79.5 [37.3-95.5], respectively), particularly in P. aeruginosa. CFD susceptibility was significantly reduced when strains were in a biofilm state. The best percentage reduction rates of all biofilm-defining variables were observed in P. aeruginosa strains.

A woman in her 20s presented with a right thumb abscess and cellulitis that failed to respond to several courses of oral antibiotics, resulting in recurrent emergency room visits over three weeks. Approximately one month after the initial skin infection, magnetic resonance imaging (MRI) revealed osteomyelitis of the right thumb. She was treated with a single dose of oritavancin (ORI) followed by two weekly doses of dalbavancin, which successfully resolved the infection. However, she subsequently developed fever and a rash consistent with DRESS syndrome, likely triggered by ORI or dalbavancin. Given the prolonged half-life of these medications, she required treatment with high-dose steroids for an extended duration. Dalbavancin and ORI are second-generation lipoglycopeptide antibiotics that provide coverage for gram-positive organisms, including MRSA. They are approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and are used off-label for bacteraemia, endocarditis, and osteomyelitis. Their prolonged half-lives—257 hours for dalbavancin and 195 hours for ORI—allow for less frequent dosing. However, a long half-life also leads to prolonged drug exposure in the event of adverse effects. Authors report the first case of DRESS syndrome in a patient treated with dalbavancin and ORI.

Oritavancin (ORI) is a new single-dose lipoglycopeptide showing in vitro activity against staphylococci and vancomycin-resistant enterococci. However, there is no data regarding its potential use as a catheter lock solution are scarce. Authors constructed an in vitro model to analyse the efficacy and stability of an ORI lock solution against the biofilm of staphylococci and enterococci over 7 days at 37 °C. They used S. aureus, S. epidermidis, and vancomycin-susceptible E. faecalis ATCC strains. Authors performed a metabolic activity assay using a 2-mg/ml solution of ORI over a 7-day incubation period at 37 °C. The solution was tested against 24-h biofilms of each strain at day 0 and 7. Metabolic activity was measured using the XTT assay, and median absorbance obtained at 490 nm in the spectrophotometer was compared between day 0 and day 7. The percentage reduction in metabolic activity was 95.3 % between biofilms treated with ORT solution incubated for 7 days and biofilms treated with ORI solution before incubation. This is a proof-of-concept study that shows ORT to be a potential treatment as a catheter lock solution for eradication of staphylococcal and E. faecalis biofilms. It is needed to further test ORI against more clinical strains and to compare its activity with other antimicrobials in a biofilm model.

Authors describe a retrospective, multicentre, observational case series of patients who received oritavancin (ORI) for treatment and/or suppressive antimicrobial therapy of VRE bone and joint infection, including osteomyelitis, native septic arthritis, myositis, and prosthetic joint infection, between December 2014 and April 2024. The minimum surveillance period was 1 year unless infection recurrence or an adverse drug event was documented before 1 year. Patients were excluded if they had a life expectancy of less than 7 days, dual use of VRE antibiotics, or brain or spinal cord abscesses related to VRE, although no patients met these exclusion criteria in our study group. Eleven patients (6 treatment, 5 suppressive antimicrobial therapy) with VRE (all E. faecium) bone and joint infection in which at least one dose of ORI was used were included. After 48 months of ORI as suppressive antimicrobial therapy, one patient in the cohort developed an infusion reaction-shortness of breath, cough, and hypotension-resulting in drug discontinuation. In this small, retrospective cohort of patients with multiple comorbidities, ORI showed possible promise as suppressive antimicrobial therapy for VRE bone and joint infection, with all patients receiving suppressive antimicrobial therapy lacking recurrence of infectious symptoms. However, the role of ORI as treatment-in salvage situations after multiple therapies failed-appeared more limited in preventing infection recurrence. Larger studies are needed to further define the role of ORI in the treatment of VRE bone and joint infections.

Epidemiological cohort study with retro- and prospective data from 01.10.2023 to 30.03.2024 including data on all ejaculates that meet the criteria of chronical bacterial prostatitis sent to University Hospital of Salzburg. Parallel to the analysis of the bacterial spectrum, the inhibitory effect of the antibiotic’s levofloxacin and delafloxacin on the pathogens found is tested. Enterococcus faecalis was the leading pathogen (46.34 % of all positive prostatitis cases). The MIC results demonstrated a better effect for delafloxacin in Gram-positive. The average MIC of Delafloxacin (0,128 µg/ml) was significant below that of Levofloxacin (5,032 µg/ml). Antimicrobial activity of delafloxacin seems a very promising treatment option for chronic bacterial prostatitis.

tested. Sánchez-Martínez C, et al. ECCMID ABSTRACT P1398

This study aims to assess the in vitro activity of delafloxacin against ciprofloxacin-resistant S. aureus (CRSA). From April 1 to October 15, 2024, 115 CRSA isolates were collected at a tertiary hospital in Madrid, including 94 methicillin-resistant S. aureus (MRSA) and 21 methicillin-susceptible S. aureus (MSSA). Isolates with ciprofloxacin MIC > 32 µg/mL had a MIC50 and MIC90 of 0.25 µg/mL and 3 µg/mL to delafloxacin, respectively. In contrast, isolates with ciprofloxacin MIC < 32 µg/mL showed MIC50 and MIC90, 0.006 µg/mL and 0.0884 µg/mL, respectively. Furthermore, we classified 34 (29.57%) isolates as resistant to delafloxacin with a median MIC value of 3 µg/m.  Delafloxacin is a highly effective quinolone but its susceptibility should always be tested against quinolone-resistant S. aureus isolates, especially if the isolate is known to have ciprofloxacin MIC values above 32 µg/mL.

31 clinical isolates of multi-resistant Gram-negative bacilli of different species were investigated in a pilot in vitro study. To determine a different in vitro effectiveness among Delafloxacin and Ciprofloxacin regarding highly drug-resistant-Gram-negative bacteria, Epsilometer-tests were used to determine minimal inhibitory concentrations of both antibiotics on bacterial pathogens like different species of the Enterobacterales-group, Pseudomonas aeruginosa and Acinetobacter baumannii in acidic and neutral environment. “Acidic” is defined a pH of 5.39 within Mueller Hinton agar, “neutral” as a pH of 7.3, which is the value according to EUCAST for routine testing. In neutral environment with a pH-value of 7,3 (standard routine testing conditions), there was no statistically significant difference in effectiveness (p = 0,814) between Delafloxacin and Ciprofloxacin regarding multidrug-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa and multidrug-resistant Acinetobacter baumannii. In acidic environment with a pH-value of 5,39, there was a statistically significant difference (p < 0,001). In acidic environment Delafloxacin exhibits lower minimal inhibitory concentrations than Ciprofloxacin in 23 out of 31 isolates (74%). Minimal inhibitory concentrations of Delafloxacin in acidic environment are in 74,2% of all tested isolates lower than those of Ciprofloxacin. Clinically this could be relevant in the antibiotic treatment of acute bacterial skin-, skin structure- and respiratory infections with lowered pH levels in the affected tissue due to inflammation.

Resistance of Corynebacterium spp. to fluoroquinolones is related to mutations occurring in the quinolone resistance determining region (QRDR) of the gyrA gene mainly, since they lack topoisomerase. The objectives of this study were to determine the minimal inhibitory concentrations (MICs) of delafloxacin, moxifloxacin, ciprofloxacin, and levofloxacin against clinical isolates of Corynebacterium spp. and to analyse the relationship between mutations in the QRDR, effect of reserpine (efflux pumps inhibitor) and the variation in MICs. Fifty-three clinical isolates (one per patient), assigned to 5 species of Corynebacterium and recovered during 2018-2022 at the Clinical Laboratory of Microbiology in Madrid. The MICs of fluoroquinolones did not decrease significantly (2 or more dilutions) in the presence of reserpine. Moxifloxacin and delafloxacin have lower MIC values than ciprofloxacin and levofloxacin against the studied isolates. Increase in the MICs of fluoroquinolones against Corynebacterium spp. are related to non-conservative mutations in the QRDR of the gyrA gene of the studied isolates.

This study aimed to investigate the in vitro activity of delafloxacin against clinical isolates of Escherichia coli (Ec) and to determine the mechanisms leading to the acquisition of resistance to this quinolone. One hundred seven clinical isolates of Ec were culture from blood samples of patients admitted to the centre (2021-2023). The isolates were selected by susceptibility to both ciprofloxacin and levofloxacin (33 resistant, 41 susceptible increased exposure and 33 susceptible). Of the 107 isolates, 43(40.2%) were resistant to delafloxacin, with a MIC range between 0.25 mg/L and >32 mg/L. In 36 of the 43(83.7%) resistant isolates, the MIC of delafloxacin decreased 4 or more dilutions in the presence of PaβN. Delafloxacin is not active in vitro against Ec resistant to ciprofloxacin and levofloxacin. An active efflux mechanism contributes to decreased activity of delafloxacin against Ec.

81 E. coli isogenic strains combining chromosomal mutations in quinolone resistance-determining regions (gyrA, parC), efflux pumps overexpression (marR) with or without plasmid-mediated quinolone resistance genes (qnrA1, qnrB1, qnrC, qnrD1, qnrS1, qepA2, aac(6′)-lb-cr) were tested. MICs of ciprofloxacin (CIP) and delafloxacin were determined via broth microdilution in Mueller-Hinton II at pH 7.3, 6.0, and 5.0 (±0.1). CIP MIC50/90 increased from 1/8 mg/L at pH 7 to 64/128 mg/L at pH 5. delafloxacin MIC50/90 decreased from 8/64 mg/L at pH 7 to 2/16 mg/L at pH 5. At pH 7, 25.9% and 8.6% of strains were susceptible (S) to CIP and delafloxacin, respectively, compared to 2.5% and 25.9% at pH 5- Mechanistic modelling revealed CIP bactericidal activity diminished at pH 5 (IC50 fold change 5/7 = 13.5 ± 11.6), while DEL activity improved (IC50 fold change 7/5 = 3.1 ± 0.5). Simulations showed DEL clinical regimens were bactericidal (-5 log10 CFU/mL at 120 h) against all strains at pH 5.  Simulations suggest DEL clinical regimens may achieve microbiological cure against low-level fluoroquinolone-resistant E. coli strains.

Prospective observational cohort study conducted from June 1, 2023, to November 15, 2024, involving all patients diagnosed with OAI and PJI who were treated with Delafloxacin in Cantabria. A total of 10 patients received oral Delafloxacin therapy, administered exclusively in an outpatient setting, with a mean treatment duration of 23.2 (±10.06) days. Surgical intervention preceded Delafloxacin therapy in 60% of cases, including debridement (40%), spacer placement (30%) and Girdlestone resection arthroplasty of the hip (10%). Microbial isolates comprised: 20% Staphylococcus epidermidis, 10% Methicillin-resistant Staphylococcus aureus (MRSA), and 40% mixed infections caused by Gram-positive cocci and Gram-negative bacilli. Delafloxacin was combined with rifampicin in 40% of cases, particularly those involving prosthetic materials. While 50% of isolates exhibited increased sensitivity to levofloxacin,20% were resistant; all isolates, however, were susceptible to Delafloxacin. At the 3,6,9 and 12-month follow-up, all patients achieved clinical, laboratory, and radiological resolution, with no adverse events reported. Delafloxacin demonstrated efficacy and tolerability as a rescue therapy in this cohort of patients with OAI and PJI, yielding high clinical success rates when combined with surgical intervention and prior intravenous antibiotic regimens

The aim of this study was to evaluate in vitro activity of delafloxacin against our quinolone-resistant isolates and anaerobes causing prosthetic joint infection (PJI). A total of 32 strains were quinolone-resistant (53% of all staphylococci isolates and 8% of all Gram-negative isolates. All quinolone-resistant strains showed lower delafloxacin MICs than levofloxacin MICs. 7 out of 16 (44%) Staphylococcus strains resistant to levofloxacin still showed susceptibility to delafloxacin (MIC50=0.38 and MIC90=1.5). All anaerobes showed low delafloxacin MICs (MIC50=0.006 and MIC90=0.064). Delafloxacin could be an interesting option for the treatment of complex PJI, including quinolone-resistant strains and PJI caused by anaerobes or polymicrobial infections including anaerobes.

This study aims to genomically characterize methicillin-resistant Staphylococcus epidermidis PJI strains. Eighteen methicillin-resistant S. epidermidis strains causing PJI1 and isolated from hospitals across Navarra during 2023 were selected for this study. All strains harboured the mecA gene. Most of the S. epidermidis belonged to ST2 (39%) and ST5 (17%) high-risk clones; all ST2 isolates presented the virulence biofilm-forming factor icaC. All quinolone-resistant strains (78%) presented QRDR mutations, 57% of these (8/14) were also resistant to delafloxacin. Higher delafloxacin MICs were observed in the presence of S84Y/F+E88K gyrA mutations, which suggests a plausible association between double gyrA point-mutations and delafloxacin resistance.

Tularaemia is a rare but emerging, contagious, vector-borne, and zoonotic infectious disease caused by the bacterium Francisella tularensis. This abstract reports a rare case of ulceroglandular tularaemia with a prolonged-relapsing course with a successful outcome. 55‑year‑old man presented with undulating fever, headache, nausea, and general weakness for about two weeks. On examination, he was found to have an ulcer-like lesion on his 3rd finger of the right hand. Initial Antibiotic treatments with Amoxicillin/Clavulanic acid and ceftriaxone showed no clinical effects. The diagnosis of ulceroglandular tularaemia was made by serology (Antibody titres against Francisella tularensis -Enzyme Immuno-Assay) in September 2022.Treatments with doxycycline and levofloxacin had no lasting effect. combined therapy with Levofloxacin and Doxycycline in early 2024 was refused by the patient after day 5 due to compatibility reasons. Therefore, we started a six-week course of Delafloxacin 450mg twice a day and Rifampicin 450mg twice a day which was well tolerated and finally led to complete resolution of symptoms. This is the first case report of a successful treatment of Tularaemia in a patient with Delafloxacin which was only tested successfully in an animal model to date. Delafloxacin could be used in the future as a highly active drug against Francisella tularensis also for a long term, well tolerated treatment.

Oritavancin use in patients with recurrent endocarditis has never been described. A 67-year-old man with a history of drug abuse was admitted to Lugano Hospital, Switzerland, in April 2022 because of persistent fever and dyspnoea. Blood cultures were all positive for E. faecalis and remained positive for 3 consecutive days. Empiric treatment was started at the time of admission with piperacillin/tazobactam plus vancomycin, then switched to ceftriaxone 2gx2 i.v. plus amoxicillin 2gx6 i.v. for 6 weeks following microbiological results and transthoracic echocardiography showing a large vegetation (17 x 11 mm) on the tricuspid valve with normal ejection fraction. Although the symptoms resolved, the patient repeatedly refused the surgical option in the post-hospital period. In October 2022, February 2023 and June 2023, the patient was repeatedly hospitalized for recurrent endocarditis, with blood cultures always positive for E. faecalis. For recurrences, antibiotic treatment included ceftriaxone 2gx2 i.v. and amoxicillin 2gx6 i.v., according to antibiogram susceptibility Cardiac function progressively deteriorated with the development of severe pulmonary hypertension, which ultimately contraindicated the surgical option. The patient refused oral suppressive antibiotic treatment; therefore, we proposed oritavancin at a dosage of 1200 mg every 10 days for 6 times as a long-term treatment option. Before each dose, we performed TDM for oritavancin with Cmin of 1.6, 2.4, 3.4, 3.6, and 4.4 mg/L, respectively. Cmin was 5.1, 2.4 and 1.2 mg/L at 2, 6 and 12 weeks after drug withdrawal. After 15 months of follow-up, the patient remained asymptomatic, and no further recurrence of endocarditis was observed. Oritavancin is a valid option for the treatment of recurrent tricuspid valve endocarditis caused by E. faecalis, especially in patients for whom surgery is not an option.

Seven cases of infective endocarditis treated with oritavancin at Policlinico Universitario “A. Gemelli” in Rome were retrieved: six men and one woman, with a median age of 75 years (61-88). Cases included prosthetic valve endocarditis (PVE, n=3), native valve endocarditis (NVE, n=3), and cardiac implantable electronic device-related endocarditis (CIED-IE, n=1) involving aortic (n=2), mitral (n=2), mitral-aortic (n=2), and pulmonary (n=1) valves. The index pathogens were Enterococcus faecium (vancomycin-resistant, n=2; vancomycin-susceptible, n=1) and Enterococcus faecalis (n=4). Median time to oritavancin administration was 27 days (range 23–82), with initial therapy tailored to the pathogen: ceftriaxone plus ampicillin for E. faecalis and daptomycin-based combinations for E. faecium. Among seven patients, three received two 1200 mg doses of oritavancin one week apart and four received a single 1200 mg dose. Overall, clinical outcomes were favourable, with all patients alive and relapse-free three months after the IE diagnosis. Of the six patients with six-month follow-up available, five remained alive and relapse-free, while one, affected by chronic congestive heart failure unrelated to endocarditis, died from pulmonary oedema following rehospitalization. This case series adds to the evidence that supports the use of oritavancin as consolidation therapy for infective endocarditis. The use of oritavancin can be beneficial to shorten length of hospitalization in uncomplicated cases and in patients who require suppressive therapy. Oritavancin appeared to be effective in challenging cases and in patients who underwent cardio-surgery interventions.

This is a single-centre observational cohort study which included adults admitted to “A. Gemelli” University Policlinic in Rome between April 2023 and May 2024 with a confirmed or possible IE caused by Gram-positive pathogens, who received at least 10 days of antibiotics. Patients who received at least one dose of dalbavancin or oritavancin following 10 days of intravenous antibiotic therapy were categorized as receiving a long-acting antibiotics-containing regimen. The primary outcome was 90-day clinical failure, defined as any of the following: IE relapse/reinfection, persistent or recurrent bacteraemia, new embolic events, unplanned surgery after discharge, or death. The study included 93 patients (mean age 77 years), of whom 62 (66.7%) didn’t receive LAAs and 31 (33.3%) received LAAs as part of their sequential therapy. The most common pathogens were S. aureus (18, 25.9%; 19.4% methicillin-sensitive, 6.5% methicillin-resistant), Streptococci spp. (18, 19.4%), E. faecalis (16, 17.2%), Coagulase-Negative Staphylococci (14, 15.1%), and S. gallolyticus (11, 11.8%). The average length of stay was 39.5 days in the non-LAAs group versus 34 days in the LAAs group. In the propensity score-adjusted multiple logistic regression model, the use of LAAs was not significantly associated with 90-day clinical failure (odds ratio 0.35, 95% confidence interval 0.1–1.18). Sequential therapy with LAAs does not appear to be associated with worse outcomes compared to standard regimens in the treatment of IE.

PK profiles from nine patients treated with multidose oritavancin for infections caused by MRSA, MRSE, E. faecalis, and E. faecium were analysed using a bicompartmental model in R with the Pmetrics package. Five patients received an initial 1200 mg dose of oritavancin, followed by 800 mg doses at weekly intervals, while four received 1200 mg doses every 14 days. Patients treated with a 1200 mg + 800 mg regimen and those who received 1200 mg + 1200 mg showed mean Cmax of 3.3 mg/L (71.1% RSD) and 131.7 mg/L (58.3% RSD), and Ctrough and Cmax of 3.5 mg/L (79.9% RSD) and 174.5 mg/L, respectively. The observed-predicted plot shows an R² of 0.878 and a slope of 1.1 (95% confidence interval). In most patients, drug concentrations surpassed the protein-binding-adjusted breakpoint value (0.83), particularly with the 1200 mg+1200 mg regimen. In contrast, the 1200 mg+800 mg regimen yielded lower-than-expected concentrations, potentially indicating reduced efficacy.

This study evaluated the clinical efficacy, bed day savings, and cost-effectiveness of off-label oritavancin use in a cohort of patients with complex infections. This retrospective case series reviewed 22 patients treated with off-label oritavancin from 2022 to 2024. Clinical cure was defined as infection resolution without recurrence within 30 days. Bed days saved were calculated based on avoided inpatient stays for daily antibiotic infusions, and cost savings were assessed by offsetting against the price of oritavancin. Staphylococcus aureus and Enterococcus faecalis were the most prominent organisms. Intravenous drug users represented 40% of the cohort. A single-dose regimen was effective in 71% of cases, while two patients required additional doses due to severe or persistent infection (two doses in a case of endocarditis with spinal abscess; three doses in a patient with joint infection). Clinical cure was achieved in 88% of patients, with no mortality observed within 30 days. The median length of follow up after administration of oritavancin was 13 days with a total estimated number of bed days saved of 393. Assuming cost of £345 per hospital day, this equates to a saving of £135,000. With the estimated cost of a single dose of oritavancin around £1,500, the total drug expense for this cohort was approximately £37,500. This represents a significant cost saving. Oritavancin demonstrates significant clinical efficacy and net cost savings in treating complex infections off-label, especially in populations with adherence challenges.

A 69-year-old patient with a history of diabetes, prostate cancer, and a right total hip arthroplasty (THA) in 2018 presented with fever following a farm-related elbow wound in October 2023. Initial oral antibiotics resolved the fever, but hip pain developed a month later. In January 14, arthrocentesis revealed purulent synovial fluid (WBC 45,000) with culture positive for MSSA, leading to a diagnosis of PJI. On January 29, he underwent PTA (Percutaneous Transluminal Angioplasty) explantation with insertion of an antibiotic-impregnated cement spacer. Empirical daptomycin with piperacillin/tazobactam was initiated. MSSA-positive cultures prompted de-escalation to daptomycin for 14 days, followed by doxycycline. On April 3, the spacer was removed, and the THA reimplanted. Negative cultures led to two weeks of intravenous oxacillin with fosfomycin and two weeks of oral ciprofloxacin. At the end of July, fever recurred with hip pain and signs of inflammation. A new arthrocentesis tested positive for oxacillin-resistant S. lugdunensis. Although the timing was suboptimal, a DAIR procedure (debridement, antibiotics, implant retention) was performed at the end of August, with 1200 mg of intraoperative oritavancin administered. Follow-up cultures confirmed the diagnosis, and two additional doses of oritavancin 800mg each were given on days 7 and 45 to extend antibiotic coverage and preserve the prosthesis. The patient responded well to the treatment and was discharged four days after the surgical procedure. Performing DAIR beyond the recommended timeframe reduces the success rate, but it remains a viable option within one month of symptom onset, especially in patients with multiple prior surgeries. Oritavancin’s PK/PD profile, high bone penetration and anti-biofilm activity, makes it ideal for intraoperative use in DAIR.

Patients with extended ABSSSI and systemic involvement, who needed admission according to clinical judgement, were evaluated by our Infectious Diseases Unit and treated with a single infusion of Dalbavancin 1500 mg or Oritavancin 1200 mg in the Emergency Department, then they underwent to a brief observation (24-48 hours) and after a documented improvement they were early discharged, with a planned follow up after 7-10 days. 14 patients were enrolled, 8 M/6 F, with average age 57 years (median 57, I.Q.R. 44 – 77). They were affected by an average of one co-morbidity (8 vasculopathy, 1 diabetes, 1 cardiopathy, 3 CODP, 2 neoplastic disease, 5 had more than 2 co-morbidities).The site of infection was the leg (11 patients), the arm (2,) flank and breast in 1. 6 patients were treated with Dalbavancin 1500 mg and 8 with Oritavancin 1200 mg, depending on availability. 9 patients were discharged, in two patients an oral antibiotic was associated (1 doxycycline, 1 cefixime). One patient had a relapse on the 30-day follow up. 5 patients were admitted to the hospital for different causes: frailty (1), co-infections (3), concomitant vein thrombosis (1). All 5 were discharged after an average hospital staying of 24 days. ABSSSIs treatment represent the on-label indication of Dalbavancin and Oritavancin. Our experience confirms the efficacy of this strategy even in moderate-to-severe patients, which showed to be useful in order to avoid hospital admissions. This strategy is useful to avoid complications, preserves patients’ health and allows to rationalize the use of the hospital admission to treat other conditions, saving medical sources.

Diabetic foot infections are typically difficult-to-treat (DTR) infections which can rapidly progress to unfavourable outcome. A 65-year-old man was admitted for right diabetic foot ulcer with second phalangeal osteomyelitis with isolation of MSSA; surgical drainage was promptly performed. Antibiotic treatment with iv cefazolin was started. Due to worsening of local condition, a trans metatarsal amputation had to be done, followed by a further debridement a few days later. MSSA was isolated in all tissue and bone culture. This time, bone culture was positive for oxacillin-resistant S. haemolyticus: antibiotic therapy was therefore changed to linezolid. The patient was discharged home 7 days later. Linezolid was later stopped due to high plasma levels and two Dalbavancin 1500 mg doses on days 1 and 8 were given. The infection recurred 2 months later with evidence of relapsing osteomyelitis; bone culture was positive for a daptomycin-resistant MRSA strain. The patient underwent leg amputation and ceftaroline was given.

This is case of a 68-year-old male with twice relapsed enterococcal bloodstream infection (BSI) and pacemaker-lead associated endocarditis (PLAE), successfully managed including extended-duration dalbavancin therapy. December 2023 elective laparoscopic cholecystectomy and biliary stent removal was performed at an outside hospital, following an episode of cholangitis one month earlier. Postoperative blood cultures (BC) revealed Escherichia coli, Enterococcus faecalis, and linezolid-resistant/vancomycin-sensitive Enterococcus faecium. Antibiotic therapy was initially started using piperacillin/tazobactam plus linezolid, then changed to amoxicillin/clavulanic acid plus vancomycin, daptomycin, and again vancomycin for a total of 4 weeks. follow-up blood culture was positive for E. faecalis, and vancomycin was restarted for suspected pacemaker-lead associated infection. The pacemaker was replaced by a temporary single-chamber system in February 2024, followed by 6 weeks of outpatient vancomycin via PICC line. In March 2024 follow-up BC again identified E. faecalis. After 3 weeks a loading dose of dalbavancin 1500 mg was given in April 2024, followed by 4 maintenance doses of 1000 mg every 2 weeks. Dalbavancin was well-tolerated, even allowing the patient to go on vacation during therapy. Blood cultures have remained persistently negative through July 2024 with no clinical sign of relapse through November 2024. This case highlights the usefulness of extended duration dalbavancin in the multidisciplinary management of a complex PLAE case. long dosing interval and favourable safety profile may make dalbavancin a valuable option also for enterococcal infections involving foreign material.

The authors describe a breakthrough bacteraemia caused by S. epidermidis in a patient with IE and spondylodiscitis with acquired resistance to dalbavancin during consolidation therapy.

A 67-year-old Caucasian male with a medical history of liver cirrhosis was admitted for L5-S1 spondylodiscitis and a definitive native aortic valve IE due to methicillin-susceptible S. epidermidis. Minimum Inhibitory Concentration (MIC, mg/L): oxacillin ≤0.25; penicillin ≥0.5; levofloxacin 4; vancomycin 2, teicoplanin 6; daptomycin 0.5, dalbavancin 0.094 and TMP-SMX ≤10)- During the MSSE breakthrough bacteraemia episode we observed progression of spondylodiscitis, enlargement of aortic vegetation with worsening aortic insufficiency, and splenic embolisms. Microbiological analysis confirmed the acquisition of resistance to dalbavancin during treatment (initial dalbavancin MIC:0.096 µg/mL, during treatment MIC:2 µg/mL). Therapeutic levels of dalbavancin resulted to be within the appropriate range (total: 40.58 mg/L; free drug: 2.84 mg/L, measured eight days after the last administration of dalbavancin). The patient was successfully treated with ceftaroline and daptomycin for six weeks with an adequate clinical and microbiological response at 12 weeks after stopping therapy. This case report highlights the potential emergence of resistance to dalbavancin in S. epidermidis IE during consolidation treatment.

All patients receiving dalbavancin as SAT were described in a monocentric retrospective observational study (07/2019-11/2024). 33 patients (23 [69.7%] males; median age, 71 [IQR, 59-80] years) received dalbavancin SAT for prosthetic joint (n=22, 66.7%), cardiovascular device-related (n=6, 18.2%) and bone/spine implant-related (n=5, 15.2%) infections. Targeted pathogens were mostly coagulase negative staphylococci (27/44, 61.4%), S. aureus (8/44, 18.2%), and streptococci (4/44, 9.1%), all isolates being susceptible to dalbavancin (MIC, 0.03 [IQR, 0.03-0.047] mg/L). Dalbavancin was used as first-line SAT in 29 (87.9%) patients (13 [61,9%] monotherapy). First dose was mostly 1500 mg (n=28, 84.8%), with a second of 1500 mg (n=19, 57.6%) administered 14 (IQR, 7-15) days after. The third administration was performed after an interval of 28 (IQR, 27–31) days (1000 mg [n=13, 39.4%] or 1500 mg [n=12, 36.4%]). Next injections were guided by therapeutic drug monitoring in most patients.

This study is to analyse whether dalbavancin is a cost-effective drug from the health-economic perspective. The healthcare cost was compared between inpatient settings and OPAT with dalbavancin. Sixty-three patients were prescribed dalbavancin in the study period; forty-one patients (65%) used in OPAT or given in DayCase Units. 53(84%) used dalbavancin for unlicensed indications and 20(32%) started without identifiable causative pathogens The total drug expenditure on dalbavancin was £18,7052.76; of which £122,690.50 (66%) was spent in OPAT. However, if the forty-one patients were treated as inpatients, it would cost the health authority 4 times as much in budget, i.e. £510,217.93 according to the cost-model of a 7-day inpatient stay comparing with OPAT setting. The study demonstrated a significant cost reduction in dalbavancin use in OPAT compared with the hospital stay with daily intravenous antibiotic. Dalbavancin provides an alternative antibiotic option to facilitate hospital discharge, reducing the need for intravenous vascular access facilities and reducing the risk of injection site infections.

The aim of this study was to investigate the clinical, microbiological and laboratory predictors of treatment failure (TF) in both on- and off-label dalbavancin treatments prescribed in our population. 351 patients who received at least one dose of dalbavancin at the Padua (Italy) centre from January 2018 to June 2024 were included. Among the treatments 54.9% were on-label and 45.1% were on off-label. The main off-label indications were osteomyelitis (17.1%), prosthetic infections (8.3%), and endocarditis (7.7%). Multivariable analysis identified several predictors of TF, including intravenous drug use (OR:4.15, p<0.01), diabetes (OR:2.1, p=0.01), obesity (OR:2.4,p=0.00), cancer (OR:1.8, p=0.01), HIV infection (OR:2.82, p<0.01), levels of CRP and procalcitonin at dalbavancin treatment initiation (OR=0.05, p<0.01 and OR=0.53, p=0.02). Additionally, for off-label use, the duration of intravenous antibiotic therapy before being discharged influenced outcomes (OR=0.52, p=0.02). Despite advantages achieved with dalbavancin use, the observed failure rate, particularly in the off label uses and among individuals with multiple comorbidities or, intravenous drug use, highlight the need for further research.

infections: a retrospective single-centre study. Barreca F, et al. ECCMID ABSTRACT P1107

This retrospective single-centre study included patients treated at Policlinico Tor Vergata, Rome, between January 2017 and June 2023 for osteomyelitis and spondylodiscitis (­including orthopaedic implant associated infections) and PJIs. Seventy patients were included, of whom 33 (47.1%) treated with dalbavancin and 37 (52.9%) with standard of care (SOC). After 6 months follow-up, 14 recovered (41.2%), 2 improved (5.9%), 4 failed (11.8%), 13 (39.4%) lost to follow-up (LTFU) in the dalbavancin treated group; in the SOC-treated group 24 patients recovered (64.9%), 4 (10.8%) improved, and 4 failed (10.8%), 5 (13.6%) LTFU. Of 70 patients, 43 (61.4%) required long-term treatment (defined as indefinite duration, potentially lifelong), due to high surgical risk that avoided implant removal or insufficient source-control: 14 (32.6%) with dalbavancin and 29 (67.4%) with SOC. The mean duration of therapy tended to be longer in the SOC group (29.2 weeks) than dalbavancin group (20.4 weeks) (p-value 0.041). Dalbavancin can represent a viable alternative for treating osteomyelitis, spondylodiscitis and PJIs both as standard timing therapy and long-term treatment in cases with insufficient source-control.

This retrospective study describes the clinical characteristics and outcomes of 54 patients with ABSSSI secondary to MRSA, who were referred to our Infectious Diseases clinic in at London, Ontario, Canada who were referred for ABSSSI between May 1, 2023, and October 30, 2024. Positive outcomes were observed in treatment with Dalbavancin in 37/54 (68.52%) patients, with 3/54 having indeterminate outcomes (presumed success as could not be reached for follow-up but were not admitted to any institution within our catchment area) and 15/54 having negative outcomes (needed further antibiotics within 44 days of following Dalbavancin). Using a single dose of IV Dalbavancin can be an effective alternative treatment for ABSSSI in patients who are at risk of nonadherence to traditional oral or IV antibiotic therapy due to complex psychosocial factors, in which positive outcomes were observed in most patients. 

This is a retrospective assessment of the outcomes of our dalbavancin use. All patients who received dalbavancin with available electronic patient records in the period 1/9/20-30/4/24 were screened, with relevant clinical and drug administration data extracted, including an assessment of clinical success (clinical resolution of infection without need for further antimicrobial treatment) and 90-day mortality. A total of 96 courses of dalbavancin given to 89 individuals were identified. 31/96 were within the licensed indication. Overall clinical success was 85.11% with a 90-day mortality rate of 6.25%. Clinical success and 90-day mortality rates for the treatment of ABSSSI without bacteraemia (87.1% and 3.23%; n=31) was comparable (p>0.99 for both measures) to that of BJI (88.9% and 5.5%; n=18) and methicillin-sensitive S. aureus (MSSA) bacteraemia (88.9% and 3.6%; n=27). Outcomes were worse for IE cases (n=12) compared with ABSSSI, with clinical success and 90-day mortality rates of 66.7% (p=0.11) and 28.5% (p=0.028), respectively. This experience highlights that dalbavancin use is likely to be similarly efficacious in some unlicensed indications compared to ABSSSI, in particular BJIs and MSSA bacteraemia, and can potentially be an ambulatory treatment option for these infections.

This retrospective, multicenter study analysed patients receiving Suppressive antibiotic therapy (SAT) with dalbavancin from 2016 to 2020. Thirty-one patients from 10 hospitals were included (median age:78 years [IQR 69-84]; 64.5% female). Dalbavancin was mostly initiated in clinics (19;61.3%). Reasons for use included toxicity from other antibiotics (48.4%), ease of adherence (41.9%), and resistance (32.3%). At analysis, 12 patients (38.7%) remained on treatment. Six patients (19.4%) failed treatment after a median of 408 days (IQR 120-521), all due to persistent infection (6;18%); no resistance development or adverse effect were observed. Three patients (9.7%) died during follow-up. Dalbavancin is proving to be a safe and convenient alternative for suppressive treatment of orthopaedic implant infections. Although the development of resistance was infrequent, it can occur and should be monitored.