This is a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality. The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. To date, this is the most extensive study evaluating real-world, postmarketing efficacy of meropenem-vaborbactam therapy for KPC-Kp infections. The overall 30-day mortality rate is 31.6% despite almost half of the patients being at high mortality risk with INCREMENT score ≥8 or admitted to the ICU at the onset of infection. The data derived from this extensive multicenter cohort lend additional support to the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy.

Authors included clinical isolates identified as S. maltophilia by VITEK 2 Compact and ceftazidime/avibactam (CZA), meropenem/vaborbactam (MVB), imipenem/relebactam (I-R), cefiderocol (CFDC), quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. 101 clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to CFDC exhibiting MIC values ≥2 μg/mL (4.95%). The β-lactamase inhibitors MVB and I-R, failed to inhibit S. maltophilia, preserving both MIC₅₀ and MIC₉₀ ≥64 μg/mL. CZA restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC₉₀. The in vitro activity of new β-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. CFDC could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.

A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.

This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (CZA), meropenem/vaborbactam (MVB), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. All data have been collected retrospectively from patient’s medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up.  This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects.

Authors included clinical isolates identified as S. maltophilia by VITEK 2 Compact and ceftazidime/avibactam (CZA), meropenem/vaborbactam (MVB), imipenem/relebactam (I-R), cefiderocol (CFDC), quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. 101 clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to CFDC exhibiting MIC values ≥2 μg/mL (4.95%). The β-lactamase inhibitors MVB and I-R, failed to inhibit S. maltophilia, preserving both MIC₅₀ and MIC₉₀ ≥64 μg/mL. CZA restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC₉₀. The in vitro activity of new β-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. CFDC could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.

In this post hoc analysis, composite, microbiologic, and clinical outcomes by cefepime-taniborbactam MIC and meropenem MIC were assessed in patients with baseline Enterobacterales and P aeruginosa from adults with cUTI in the Phase 3 CERTAIN-1 study. Taniborbactam decreased the cefepime MIC90 by 2,048-fold (to 0.25 mg/L) against Enterobacterales overall, by ≥1,024-fold (to 1 mg/L) against cefepime resistant, ESBL. and MDR subsets of Enterobacterales, by ≥128-fold (to 8 mg/L) against CRE, and by 2-fold (to 16 mg/L) against P aeruginosa. Cefepime-taniborbactam demonstrated potent in vitro activity against baseline isolates of Enterobacterales and P aeruginosa from patients in the Phase 3 CERTAIN-1 study. Few patients had baseline isolates with elevated cefepime-taniborbactam or meropenem MICs

This study reports on the susceptibility of a recent (2018–2022} European collection of clinical isolates of Enterobacterales (n=941) and P. aeruginosa (n=841)  of cefepime- taniborbactam and comparator  agents stratified by their beta-lactamase content. The addition of taniborbactam to cefepime greatly enhanced its in vitro activity against most isolates of Enterobacterales carrying NDM (75%) and VIM-type (94,6%) metallobetalactamase-. Cefepime taniborbactam also demonstrated potent antimicrobial activity against enterobacterales harboring KPC (100%), OXA 48-group (99,3%), ESBL (96,2%) and acquired ampC type enzyme 96.2 %. Moreover, this agent was also the most active agents against P. aeruginosa harboring GES (100%), VEB (91,9%) and PER (100%) type enzyme.

This study evaluated the activity of cefepime-taniborbactam and comparator agents against resistant clinical isolates of Enterobacterales (n=8760) and P. aeruginosa (n=3480) isolates in Europe from a 2018-2022 global Surveillance study. The addition of taniborbactam to cefepime greatly enhanced its n vitro activity against Enterobacterales and P. aeruginosa from European sites, including most isolates nonsusceptible or resistant to cefepime, meropenem, piperacillin tazobactam, ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam

Study’s authors compared the in vitro activity of ceftazidime-avibactam (CZA), imipenem-relebactam (IRL), and meropenem-vaborbactam (MVB) against both CRKP and CRPA clinical isolates. Minimum inhibitory concentrations (MICs) for each agent were determined using broth microdilution. While CZA and MVB showed comparable susceptibility to IRL against CRKP (93.8%), susceptibility of CRPA to CZA was modest at 79.2%, whereas most CRPA strains were resistant to MVB. Of the 35 CRKP isolates tested, 91.4% (32/35) carried a blaKPC gene. Only 1 of 37 (2.7%) CRPA isolates tested carried a blaVIM gene, which conferred phenotypic resistance to all three agents. None of the CRKP strains were cross-resistant to all three agents. Source of infection and co-infection did not significantly influence antimicrobial activity for IRL and CZA; none of the CRPA isolates from co-infected patients were susceptible to MVB. Study’s results suggest that novel β-lactam agents with antipseudomonal activity and stability against carbapenemases, such as IRL and CZA, offer potential monotherapy options for the treatment of co-infection involving both CRKP and CRPA, but not MVB

Study’s aim was to evaluate the antimicrobial susceptibility of Enterobacterales causing BSI in US medical centres and compare the activity of aztreonam-avibactam (ATM-AVI) with ceftazidime-avibactam (CZA), meropenem-vaborbactam (MEV), imipenem-relebactam (I-R), cefiderocol (CFDC), and other antimicrobials used to treat BSI. 4,802 Enterobacterales were consecutively collected (1/patient) from 72 US medical centres in 2020–2022. ATM-AVI was tested with avibactam at a fixed 4 mg/L and was highly active against Enterobacterales; only 2 isolates showed ATM-AVI MICs > 8 mg/L: 1 meropenem-susceptible E. coli and 1 K. aerogenes (CRE). ATM-AVI retained activity (MIC, ≤ 8 mg/L) against all (100.0%) meropenem-vaborbactam non-susceptible (n = 17), 99.5% of I-R non-susceptible (n = 206), and 90.0% of CZA non- susceptible (n = 10) isolates. The most common carbapenemases were KPC-2/3 (57.1% of CREs), OXA-48–like (16.3%), and NDM (14.3%). A carbapenemase gene was not observed in 12.3% of CREs. CZA and MEV were active against 100.0% of KPC producers, but CZA showed limited activity against MBL producers and MEV showed limited activity against OXA-48–like and MBL producers. The most active non–βlactam comparators against CRE were gentamicin (49.0% susceptible) and amikacin (44.9% susceptible). ATM-AVI demonstrated potent activity against Enterobacterales isolated from patients, with BSI in US hospitals.

Increased Klebsiella pneumoniae resistance to carbapenems and β-lactams, has become one of the main causes of septicaemia, pneumonia, and urinary tract infections. This study aims to report the prevalence and antibiotic resistance rates of K. pneumoniae strains isolated from clinical specimens from 2015 to 2020 at the University Hospital of Salerno, Italy. More than 3,800 isolates were collected from urine cultures, blood cultures, respiratory samples, and others. K. pneumoniae isolates showed broad resistance to penicillin and cephalosporins, and increased susceptibility to fosfomycin and gentamicin. Extended spectrum beta-lactamase (ESBL) isolates accounted for 20–22%. A high percentage of strains tested were resistant to carbapenems, with an average of 40% to meropenem and 44% to ertapenem.

From June 2019 to Dec. 2023, a retrospective observational study of kidney transplant (KT) recipients with CR-GNB infection treated with CZA was conducted, with the primary outcome being 30-day mortality. Risk factors for 30-day mortality and clinical failure were also investigated. A total of 81 KT recipients treated with CZA were included in this study. 40 recipients (49.4%) received CZA monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CZA alone or in combination with other medications had no effect on clinical cure or 30-day mortality, but clinical cure was positively associated with the administration of CZA within 48 h of infection onset and negatively associated with higher APACHE II scores. CZA is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy and optimization of CAZ/AVI therapy is positively associated with potential clinical benefit.

This analysis of REVISIT data focuses on clinical and microbiological efficacy by baseline pathogen resistance types. Among 271 patients included in the micro-ITT analysis set (aztreonam-avibactam; n=177; meropenem, n=94), the most frequent baseline pathogens were Enterobacterales, identified in 93% of patients overall. Most patients (64%) had monomicrobial infections All tested baseline Enterobacterales isolates (n=272) had aztreonam-avibactam MIC ≤8 mg/L; 7.7% and 26.8% were non-susceptible to meropenem and aztreonam, respectively. Clinical and microbiological responses at TOC were generally consistent between aztreonam-avibactam and meropenem across baseline pathogen resistance subtypes. Patients with MBL-producing pathogens treated with aztreonam-avibactam who had clinical failure also tended to have previous antibiotic treatment failure and complex medical history.

The in vitro activity of aztreonam-avibactam against 94430 Enterobacterales isolated clinically from 2018-2022 across global regions of Africa, Asia, Europe, Latin America, Middle East, and South Pacific was evaluated. Aztreonam-avibactam demonstrated potent in vitro activity against Enterobacterales isolates collected from the different regions examined, while susceptibility of isolates to comparators varied by region with no comparator active against >90% of isolates from every region.

The in vitro activity of aztreonam-avibactam against 21644 Enterobacterales isolates from patients in intensive care units (ICU) and non-ICU wards from 2018-2022 was assessed. Based on MIC90values and the putative PK/PD breakpoint of 8 mg/L, aztreonam-avibactam demonstrated potent in vitro activity against Enterobacterales isolates collected from patients in both ICU and non-ICU wards, including those that carry MBLs.

The in vitro activity of aztreonam-avibactam against MBL-positive Enterobacterales collected in 2018-2022 through the ATLAS Global surveillance program was evaluate. MIC90 values demonstrated potent in-vitro activity of aztreonam-avibactam against isolates of Enterobacterales harbouring MBLs.

This study examined the in vitro activity of aztreonam-avibactam and comparators against Enterobacterales with multi-drug resistant phenotypes collected worldwide in 2018-2022 as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) global program. Aztreonam-avibactam exhibited excellent in vitro activity against multidrug-resistant subsets of Enterobacterales based on low MIC90values. These data support continued development of aztreonam-avibactam as a promising therapy for difficult-to-treat infection.

The Phase 3 ASSEMBLE study evaluated the efficacy and safety of aztreonam-avibactam and best available therapy in adults with cIAI, HAP/VAP, complicated urinary tract infection (cUTI) or bloodstream infection (BSI) caused by MBL-producing Gram-negative bacteria. ASSEMBLE was a Phase 3, prospective, randomised, open-label, parallel group, multicentre, comparative study with patients enrolled at 12 sites in China, Greece, India, Malaysia, Mexico, Philippines, Romania, Russian Federation and Thailand. Patients in the aztreonam-avibactam group received a 500-167 mg aztreonam-avibactam loading dose (30-min infusion), followed immediately by a 1500-500 mg extended loading dose (3-h infusions), and then 1500-500 mg maintenance (3-h infusions) doses q6. The primary efficacy endpoint was clinical cure at the test-of-cure (TOC) visit in the microbiological intent-to-treat (micro-ITT) analysis. In total, 15 patients (mean age 58.4 years, 60% male) with ≥1 MBL-positive Gram-negative pathogen were randomised (12 to aztreonam-avibactam and three to best available therapy) and included in the micro-ITT analysis set. Clinical cure rates at TOC were 41.5% (5/12) for aztreonam-avibactam and 0% (0/3) for best available therapy. All-cause 28-day mortality rates were 8.3% (1/12) for aztreonam-avibactam and 33.3% (1/3) for best available therapy. These data suggest a potential role for aztreonam-avibactam for treating serious infections caused by MBL-producing Gram-negative bacteria, for which few treatment options are currently available.

The aim of the study was to provide susceptibility data that support informed decisions for empirical therapy in case of suspected presence of carbapenemase positive Enterobacterales. Isolates of different Enterobacterale species that were submitted to the NRC in the years 2021 and 2022 were analyzed for their susceptibility to aztreonam-avibactam, ceftazidime-avibactam, meropenem and cefiderocol by microdilution (Micronaut-S E1-362-100 and UMIC Cefiderocol, Bruker) and for cefiderocol also by agar diffusion. Aztreonam-avibactam showed lower resistance rates than ceftazidime-avibactam or cefiderocol

The aim of this study was to evaluate the PK of these new beta lactams administered by Cl in the plasma and epithelial lining fluid (ELF) in 16 critically ill patients with nosocomial pneumonia. Statistical differences between concentrations of both antibiotics were found at any time point measured. The median (IQR) ELF penetration ratio was 38.9 % (20.2-44.8} in the CTZ group and 46.S % (33.8-77.1) in the CFT group (p = 0.29). Continuous infusion allowed for high lung penetration of ceftazidime/avibactam and ceftolozane/tazobactam with concentrations in ELF above 4 times the MIC for all susceptible strains and no differences between the two beta lactams

This study evaluated the in vitro bactericidal activity of ceftazidime in combination with incremental concentrations of avibactam against ceftazidime/avibactam susceptible and/or -resistant KPC-producing K. pneumoniae. In vitro evaluation of increasing concentration of avibactam in presence of ceftazidime showed high activity against susceptible strains. High concentrations of avibactam hardly reached in vivo are required to be active against resistant KPC-producing K. pneumoniae.

This study investigates the induction of resistance to cefiderocol in patients with carbapenem resistant infections during ceftazidime-avibactam (CZA) based treatments. All patients were administered CZA for a median time of 25 days, and developed resistance within a median time of 23 days of exposure. Following CZA -based regimen, the median MIC for CZA increased from 2 μg/ml (IQR: 2-8 μg/ml) to 256 μg/ml (IQR: 256-256 μg/ml). In addition, all patients showed an increase in MICs for cefiderocol, with a median value of 2 μg/ml (IQR: 1-2 μg/ml) rising up to 16 μg/ml (IQR: 8-16 μg/ml). Treatment based on CZA may have led to the acquisition of mutations in KPC correlated not only with CZA resistance, but also with cefiderocol resistance. This finding highlights the risk of cross-resistance emergence during CZA -based therapy.

 In this study, authors investigated the in vivo evolution of resistance to ceftazidime-avibactam in longitudinally intra-patient carbapenem resistant Klebsiella pneumoniae (CRKP) strains obtained from a single patient. This results revealed the rapid in vivo development of KPC mutations conferring resistance to CZA and the high adaptability and competitive advantage, which highlights the potential threat of CRKP.

The study aimed to assess the clinical features, antibiotic therapy and outcomes of 55 neutropenic cancer patients with bloodstream infections (BSI) due to CRE treated with CZA. In this real-life experience, CZA was used in onco-hematologic neutropenic patients with BSI due to CRE. CZA showed to be safe and efficacious for the treatment of these extremely high-risk patients.

In this study, we evaluated the efficacy of ceftazidime-avibactam and colistin in combination against a clinical KPC-2-producing K. pneumoniae strain with porin deficiencies. Synergistic and bactericidal effects were observed with ceftazidime-avibactam in combination with colistin at clinically relevant concentrations against a clinical KPC-2-producing K. pneumoniae strain.

The aim of this study was to investigate the pharmacokinetics (PK) of CAZ and AVI in critically ill patients undergoing CVVHDF (continuous veno venous hemodiafiltration), comparing the results with a phase III trial population. Two frequently used intermittent dose regimens (2000/500 or 1000/250 mg given every 8 hours as 2h-infusion) were evaluated. The contribution of CAZ & AVI drug removal by CVVHDF was characterized. The investigation revealed flatter CZA PK profiles in comparison to typical profiles in phase III population, due to increased volumes of distribution in patients undergoing CVVHDF. Despite distinctive PK profiles (characterized by lower peak concentrations and elevated troughs), selected dose regimens (2000/500 or 1000/250mg q8h)appeared to be well-tolerated and effective in maintaining therapeutic concentrations during CVVHDF.

This study aims to analyze the relationship between administered ceftazidime-avibactam dosage and plasma concentrations in 7 ECMO (extracorporeal membrane oxygenation support) patients. Secondary objectives include investigating drug retention within the ECMO circuit. In 86% of patients, the recommended ceftazidime-avibactam exposure was achieved with the administered doses. Thus. ECMO-treated patients with ceftazidime-avibactam appear not to require dose adjustments for desired plasma concentrations, and the drug does not accumulate in the circuit. However, further cases are needed for reliable data and conclusions.

15 K. pneumoniae CZA-resistant strains isolated in the Intensive Care Unit {ICU) of the Mediterranean Institute for Transplants and highly specialized Therapies (ISMETT) located in Palermo (I), were studied. In the isolates, CZA resistance was associated with mutation in bla_KPC (bla_KPC31 and bla_KPC34), Over expression of blaKPc-3, strains harbored: a plethora of plasmids and mutations in genes encoding for porins. Deep molecular approaches are required for K. pneumoniae KPC-producing infections in order to establish effective control measures, optimize therapies and mitigate the impact of multidrug-resistant pathogens in healthcare settings.

This is multicentre, open label, randomised trial comparing cefiderocol with standard of care (SOC) antibiotics in 514 patients with hospital-acquired or healthcare-associated BSI caused by gram negative bacilli. Participants were randomised <48 hours post initial blood culture collection 1:1 to cefiderocol (2 grams over 3 hours, frequency determined by renal function) or SOC, as determined by the treating team. The primary outcome was all-cause mortality at day 14. 20/250 (8.0%) patients randomized to cefiderocol met the primary outcome of mortality at 14 days, compared with 17/254 (6.7%) randomized to SOC (risk difference 1.3%, 95% CI: -3.2% to 5.9%; RR 1.20 95% CI: 0.64 to 2.23), demonstrating non-inferiority. Cefiderocol for hospital-acquired or healthcare-associated gram-negative BSI was non-inferior, but not superior, to SOC.

This ongoing, international, retrospective, medical chart review study to describe usage of cefiderocol, post commercialisation, for the treatment of 129 patients with Gram-negative bacterial infections from 10 French centres, who were included in the ongoing PROVE study. This large cohort of real-world evidence post commercialization of cefiderocol in France showed that cefiderocol was used primarily to treat respiratory infections and non-fermenter pathogens, including mainly Pseudomonas spp. A large proportion of patients responded to cefiderocol treatment and mortality rates overall were approximately 15% and 20% at days 14 and 30.

In this study, a cefiderocol susceptibility testing of clinical Kp isolates was performed to explore the prevalence of cefiderocol -resistant isolates and the mechanism of cefiderocol -resistance on 2 isolates that represented cefiderocol -resistance. The amplification of bla_shv-12 and the consequent dynamic within-host hetero resistance are important concerns for the rational application of antibiotics. Long-read sequencing might be a superior way to detect resistance gene amplification rapidly and accurately.

This study assessed the cefiderocol in vitro susceptibility of a recent panel of 246 multidrug-resistant (MDR) Enterobacterales clinical isolates from countries with high burden of antimicrobial resistance. Cefiderocol showed the best susceptibility profile against all Enterobacterales with a MIC50 and MIC90of 2 and 4 mg/L , respectively. Among CR isolates (n=919), susceptibility to cefiderocol was higher than to any other tested antibiotic, with rates of 87.6% (n=805/919) and 62.4% (n=573/919) .Susceptibility to cefiderocol was higher among K. pneumoniae isolates, 95.9% (n=722/753) and 76.5% (n=575/753), according to CLSI and EUCAST recommended breakpoint concentrations, respectively.Non-susceptibility to cefiderocol was higher among NDM-producing Providencia rettgeri, Enterobacters spp and E. coli isolates. This study confirms the potent in vitro activity of cefiderocol against MDR/CRE isolates from regions with high prevalence of Enterobacterales with metallo-β-lactamases and OXA-48-like carbapenemases and suggests that cefiderocol could be considered as a therapeutic option in countries with high burden of infections caused by CREs.

The aim of this study was to evaluate the impact of the PBP3 modification on susceptibility to ceftaddime-avibactam (CZA), imipenem relebactam (I-R), cefiderocol, aztreonam-avibactam and cefepime-taniborbactam using a series of isogenic E. coli recombinant strains producing a wide range of Beta-lactamases. This work highlights the potential impact of the PBP3 modification in acquired-broad spectrum beta•lactamases producing E. coli on susceptibility to last-line treatments, not only for aztreonam-avibactam as previously reported in several studies, but also for CZA, cefepime-taniborbactam and to some extent, meropenem vaborbactam and cefiderocol. However, a notable exception was observed with imipenem-relebactam that was not affected by the PBP3 mutations tested in this study.

This in vitro study was conducted in 40 strains of P. aeruginosa isolated from 30 French hospitals.There was a diversity of resistance mechanisms in clinical strains of P. aeruginosa to cefiderocol. Moreover, a high-levels of resistance to cefiderocol are due to a combination of intrinsic mechanisms and the acquisition of β-lactamases

This was a retrospective multi-centre cohort including 98 adults with active solid cancers (SC), haematological malignancies (HM), hematopoietic stem cell transplantation (HSCT), solid organ transplantation (SOT), interstitial lung disease (ILD) under immunosuppressant and treated with cefiderocol between 01/01/2020 and 30/10/2023 upon multidrug-resistant GNB infection. The primary objective was to evaluate clinical success at days 28 and 90. At day 28, 56/98 (57%) infections were resolved, in addition of 8 more by day 90. At day 28 and 90, persistent infection was recorded in 7/63 (11.1%) and in 4/45 (8.8%) alive patients, respectively. In this series, a trend towards the use of cefiderocol for severe colistin-susceptible Pseudomonas infections in immunocompromise was observed.

Cefiderocol (FDC) and ceftazidime-avibactam (CZA) demonstrate potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp); however, treatment-emergent resistance to CZA is well-documented. The objective of this study was to assess the impact of KPC variants and ompK36 porin genotypes on the in vitro activity of FDC. FDC MICs are increased among clinical Kp isolates harboring KPC variant enzymes conferring resistance to CZA. CZA-FDC MIC correlations in isogenic E. coli harboring each blaKPC genotype was confirmed. Surprisingly, FDC MICs, but not CZA MICs, are impacted by ompK36 mutations. These data suggest that porin channels may play an important role in FDC access to the periplasmic space against KPCKp.

Ceftazidime/avibactam (CZA), a novel β-lactam/β-lactamase inhibitor combination, effectively targets bacteria that are resistant to serine β-lactamases. However, mutations in the Ω-loop region of some β- lactamases, like KPC, CTX-M, confer resistance to CZA. The flexibility of enzymatic activity in β-lactamase variants, along with the heterogeneity mediated by plasmids or multicopy genes within the population, contributes to the complexity of multidrug resistance evolution. novel β-lactamase CTX-M-65 variant, CTX-M-249 (Ser133Gly & Pro170Ser), was identified from a clinically isolated Klebsiella pneumoniae and conferred resistance to CZA along with decreased cefotaxime activity. In this study, a clinically isolated K. pneumoniae displaying a heterogeneity caused by dual-copy blaCTX-M- 65 variants located on the same plasmid and mediating resistance to multidrugs, including ceftazidime/avibactam was reported. This so-called bet-hedging strategy vastly extended the evolutionary fitness advantage against potential multidrug pressures, particularly in nosocomial environments compared its ancestor.

Assessment of Oritavancin (ORI) in vitro activity against clinically relevant Gram-positive pathogens in European (EU) hospitals, in a total of 51,531 consecutive and unique clinical isolates. ORI inhibited 99.9% and 99.1% of all S. aureus and coagulase-negative staphylococci at 0.12 mg/L, respectively, and all isolates of E. faecalis and E. faecium at ≤0.5 mg/L. ORI susceptibility rates against β-hemolytic and viridans group streptococci isolates were 98.1% and 99.4%, respectively.

The objective of the study was to evaluate in vitro activity of oritavancin on clinical isolates of Enterococcus faecium VRE and to compare the distribution of minimum inhibitory concentrations (MICs) with those reported by EUCAST for Enterococcus faecium strains. The MIC range of oritavancin for the 57 isolates was 0.06 mg/L to 1 mg/L and the MIC50 and MIC90 values were 0,25 mg/l and 0,5 mg/L respectively. This results, together with clinical efficacy data from the use of oritavancin in Enterococcus faecium infection, may contribute to the definition and robustness of the currently and available data.

This study evaluated the susceptibility patterns and the in vitro activity of oritavancin against an 18 isolates of vancomycin-resistant (E. Faecium) collected at Hospital Universitario Miguel Servet (Zaragoza, Spain) . According to the CLSI breakpoints (susceptibility MICs .s 0,12 mg/L), oritavancin inhibited 94% of 18 isolates (MIC 50 0,016/MIC 90 0,12 mg/l). Oritavancin displayed potent MICs against vancomycin-resistant E. faecium. These in vitro results suggest that oritavancin can provide a promising therapy for vancomycin-resistant E. faecium complicated infections.

Oritavancin has a potent activity against Vancomycin-resistant Enterococci (VRE) and linezolid resistant (LR) ones. The abstract reports a clinical case of a 46- years old patient with liver abscesses by LR-VRE treated with off-label oritavancin. This is the first described case of liver abscesses by LR-VRE treated with off-label oritavancin, and the first reported strain co-producing VanA, OptrA, and CfrD, isolated from bloodstream infection. In setting with limited options, such as LR-VRE infections, oritavancin could be a valuable alternative with a good in vitro and in vivo activity.

Delafloxacin is a recently developed fluoroquinolone, with an extended spectrum against most staphylococci, which could be a promising option for staphylococcal Bone and Joint infections (BJI). In this context, this work aimed to evaluate the activity of delafloxacin against strains isolated from BJI, particularly in the biofilm and intracellular setting. Delafloxacin showed good in vitro activity against levofloxacin-susceptible S. aureus, whether planktonic, in biofilms or internalized in osteoblasts. Its activity was also good against levofloxacin-resistant strains in the planktonic state, but in biofilm and intracellularly in osteoblasts its activity was strain-dependent despite the same MIC. The antibiofilm and intracellular activity of delafloxacin against the 6850 levofloxacin-R strains was not greatly affected, probably because the mutations conferring fluoroquinolone resistance in this strain only affected the parC gene. This study confirms the potential interest of using delafloxacin in the context of However, its use needs to be carefully monitored in order to maintain its efficacy and limit the emergence of resistance.

Delafloxacin exerts several promising features: an enhanced activity at low pH1 and a nearly equivalent affinity for both type-II topoisomerases, potentially preventing the emergence of bacterial resistance. Since the pH of urine is usually acidic, Delafloxacin could be an interesting alternative for the treatment of male urinary tract infections (UTls), especially those caused by enterococci. The aim of this study was to evaluate ln vitro 1) the activity of Delafloxacin under urine mimicking acidic conditions against 9 Enterococcus faecalis clinical isolates responsible for male UTls and 2) the frequency of selection of resistant mutants in such species. Delafloxacin demonstrates enhanced in vitro activity compared to levofloxacin and moxifloxacin, especially at low pH values as well as a limited potential of emergence of resistance. Altogether, it demonstrates a potential clinical utility of Delafloxacin in the treatment of difficult-to-treat enterococcal male UTls, which must be confirmed in vivo.

This experiment aimed to determine the activity of delafloxacin against invasive isolates of S. pneumoniae resistant to levofloxacin (LEV-R). it also describes mutations in gyrA, parC,and parE genes, and compares delafloxacin MICs of LEV-R isolates with these of susceptible isolates. Among levofloxacin resistant Streptococcus pneumoniae isolates, 14.3% (12/84) were also resistant to delafloxacin. Resistance to delafloxacin was associated with the accumulation of at least 2 mutations in gyrA.

This retrospective cohort study describes the characteristics, treatment rationale and outcomes for 58 adult inpatients treated with dalbavancin at a UK tertiary hospital. Acute bacterial skin and skin structure infection, infective endocarditis and endovascular infections were each diagnosed in 22.4% of patients. Bone and joint infections were diagnosed. Thirty-five patients (60.3%) were PWID, with low median age (41.0 years) and Charlson Comorbidity scores (0). Treatment was successful in 43 (75.4%) patients, and failed in seven (12.3%). In this first UK cohort, dalbavancin was used off licence and in persons facing barriers to conventional therapies. Where data is available, it was safe and effective.

In this study, resistance to ceftaroline, vancomycin and daptomycin was studied in 100 MRSA strains isolated from blood cultures and skin/soft tissue (SSTI) samples. In addition, the in vitro effectiveness of ceftaroline in combination with vancomycin and daptomycin against ceftaroline-resistant isolates was investigated. Based on this results, new synergistic antimicrobial combinations are needed, since combinations of ceftaroline with daptomycin and vancomycin resulted in indifference effect. Further studies in which ceftaroline will be combined with meropenem and linezolid are planned.

According to EUCAST expert rules, S. aureus isolates susceptible to vancomycin can be reported susceptible to dalbavancin, and according to French AST recommendations (CASFM), staphylococcal strains susceptible to vancomycin are susceptible to dalbavancin regardless of species. The study tested this assumption in the context of clinical practice, performing antimicrobial susceptibility test on 22 agents by broth microdilution in 2,202 staphylococcal strains. Overall, 158 strains (7.2%) were resistant to dalbavancin. The authors conclude that susceptibility to vancomycin is not a valuable surrogate for susceptibility to dalbavancin. A better surrogate appears to be susceptibility to teicoplanin. Resistance to teicoplanin is not a predictor of resistance to dalbavancin but should be a warning of possible dalbavancin resistance. In practice, contrary to current EUCAST and CASFM expert rules, not all staphylococcal strains susceptible to vancomycin appear to be susceptible to dalbavancin. In case of clinical use, dalbavancin MIC should be determined systematically, especially if the isolate is resistant to teicoplanin.

This retrospective, observational, multicenter study that enrolled 235 patients treated with Dalbavancin(35% of off-label use of Dalbavancin) from 1 January 2019 to 30 September 2023 aimed to evaluate therapeutic success (clinical cure or infection control if chronic suppress therapy) and adverse events (AEs) for dalbavancin on-label and off-label indications. In the on-label group, dalbavancin was mainly used as an empirical therapy (62.2%), while in the off-label group as a targeted therapy for MRSA (31%) and/or as a combination therapy. Dalbavancin was widely used for on-label and off-label indications with a success rate of 82.8% and 73.5%, respectively, and a good safety profile.

Alternative to vancomycin linezolid, daptomycin, and dalbavancin are frequently used and were therefore evaluated in terms of possible MRSA resistance causes in this analysis of 55 MRSA bloodstream isolates. In this analysis, two novel missense mutations (p.1515M and p.A606D) in the pbp2 gene were found to be potential origins of dalbavancln resistance. Furthermore, based on the observed dalbavancin MIC creep, inclusion of dalbavancin in routine antimicrobial susceptibility testing should be considered.

This study was a multicenter, randomized, assessor-blinded trial comparing dalbavancin to standard of care (SOC) therapy for 200 adults with complicated S. aureus bacteremia (SAB), including right-sided endocarditis, to evaluate if dalbavicin is safe and effective in this patients. Subject with bacteremia following ≥72 hours but ≤10 days of initial antibacterial therapy were randomized 1:1 to receive either two doses of dalbavancin (1500 mg on days 1 and 8) or 4-8 total weeks of SOC (generally cefazolin or nafcillin if methicillin-susceptible; vancomycin or daptomycin if methicillin-resistant). The primary outcome was desirability of outcome ranking (DOOR) at day 70 by intention to treat (ITT), which includes the cumulative incidence of clinical failure, infection complications, serious adverse events (SAEs), AEs leading to study drug discontinuation, and mortality. The probability of a more desirable day 70 outcome with dalbavancin versus SOC was 47.7% (95% CI: 39.8-55.7%). While dalbavancin was not superior to SOC, it showed a similar benefit/risk profile to SOC by DOOR and was non-inferior to SOC by traditional clinical efficacy endpoints for complicated SAB