This case report illustrates the treatment course of CTX-M and KPC-producing Klebsiella pneumoniae, and Bacillus species bacteremia that included cefiderocol, followed by vancomycin and meropenem-vaborbactam, and then meropenem-vaborbactam monotherapy. The patient was a 74-year-old female who had a prolonged hospital course and several courses of intravenous antimicrobials prior to the multidrug resistant (MDR) Klebsiella pneumoniae, and Bacillus species bloodstream infection. The IDSA does not have treatment recommendations for Bacillus species, though the Clinical & Laboratory Standards Institute (CLSI) reports breakpoints for vancomycin and meropenem. In our case, the patient’s Bacillus isolate was susceptible meropenem-vaborbactam (0.023 mcg/mL) based on a meropenem breakpoint of 4 mcg/mL. In our report, an immunocompetent patient developed a polymicrobial bloodstream infection caused by an MDR Klebsiella pneumoniae, and Bacillus species, which was successfully treated with meropenem-vaborbactam. This unusual infection and treatment course also serves to promote awareness of another treatment option for invasive Bacillus species infection and furthermore encourages providers to request testing & sensitivities to consolidate therapy, particularly in cases of polymicrobial infection.

This study assesses the activity of humanized serum concentrations for meropenem (2 g Q8h), meropenem-vaborbactam (4 g Q8h), and ceftazidime-avibactam (2.5 g Q8h) against carbapenemase-producing (CP) and non-CP Enterobacter cloacae isolates in a 120h in vitro pharmacodynamic model. Additionally, authors compared antimicrobial administration as a bolus or extended infusion for each isolate and treatment. For the CP strain, all treatments with meropenem-vaborbactam and ceftazidime-avibactam were bacteriostatic through 24 h. Extended-infusion meropenem-vaborbactam exhibited the most prolonged bacteriostatic activity and was significantly more effective than ceftazidime-avibactam at 120 h. For the non-CP strain, all simulated treatments demonstrated initial bactericidal activity through 24 h, except for ceftazidime-avibactam bolus administration. Meropenem and meropenem-vaborbactam, administered as bolus dosing, each maintained significantly greater bacterial colony count reductions compared to extended infusion through 120 h against non-CP CRE (P < 0.01). No significant differences were found between bolus and extended infusion for ceftazidime-avibactam (P = 0.08). Resistance development was observed following treatment with meropenem monotherapy (minimum inhibitory concentrations increasing to >32 µg/mL for the non-CP isolate with extended infusion and to >32 µg/mL for the CP isolate with bolus and extended-infusion treatments) and ceftazidime-avibactam. Meropenem-vaborbactam exposure did not result in the emergence of antimicrobial resistance in any of the tested models.

This study evaluated the in vitro efficacy of eravacycline and the potential synergistic activity of meropenem-vaborbactam in combination with either gentamicin or ceftazidime against carbapenemase-producing A. baumannii isolates (CRAB). A total of 25 CRAB isolates were collected from different clinical samples. Antimicrobial susceptibility was determined via disc diffusion. Meropenem was tested by both disc diffusion and gradient strips. Extensively drug-resistant (XDR) CRAB isolates were selected for evaluating colistin, eravacycline and the in vitro synergy of antimicrobial combinations via gradient strips for meropenem-vaborbactam, gentamicin, and ceftazidime. All CRAB isolates were sensitive to tigecycline and were either multidrug resistant or XDR. The minimum inhibitory concentrations (MIC50s and MIC90s) of meropenem were 32 μg/mL and 256 μg/mL and the MIC50 and MIC90 of eravacycline were 0.125 μg/mL and 0.5 μg/mL, respectively. Meropenem-vaborbactam in combination with ceftazidime or gentamicin showed synergy in 45.5% and 36.4% of the XDR isolates and additivity/indifference in 54.5% and 63.6% of them, respectively, with no antagonism. Authors findings suggest that eravacycline, as well as combination therapies involving meropenem-vaborbactam with either gentamicin or ceftazidime, may offer promising therapeutic potential for CRAB infections pending further clinical evaluation. These agents demonstrated notable in vitro activity, including potential synergistic effects, particularly against isolates harbouring carbapenemase enzymes.

This is a structured review of the sodium content of novel antibiotics in nephrology, based on approved Summary of Product Characteristics. Standard dosing regimens were used to estimate daily sodium burden in adult patients. Clinical implications were contextualized for patients with chronic kidney disease with or without dialysis. Substantial variability in sodium content exists across novel antibiotics. High sodium content of > 3 g/day at standard dosages must be considered with fosfomycin and meropenem/vaborbactam. A sodium load of 1.5 g/day up to 3 g/day is associated with therapy with ceftolozane/tazobactam, cefiderocol, delafloxacin, imipenem/cilastatin/relebactam, and ceftazidime /avibactam at standard dosages utilizing sodium chloride as diluent. For the latter antibiotics, the alternative use of dextrose solutions as diluent reduces significantly the sodium load to values below 1.5 g/day. Eravacycline, lefamulin, ceftaroline fosamil, tedizolid, dalbavancin, and oritavancin itself contain an insignificant amount of sodium; only the diluent, such as sodium chloride, sodium citrate buffer, or Ringer lactate, contributes to a daily sodium load of less than 2 g/day. Parenteral antibiotics are an often-overlooked contributor to sodium intake. Clinicians should be aware of this hidden source in sodium-sensitive patients such as kidney disease patients. Authors propose a visual chart to support sodium-conscious antimicrobial selection as part of broader stewardship strategies.

This study aimed to investigate the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), elucidate the resistance mechanisms to ceftazidime-avibactam (CZA) and identify the risk factors associated with CZA resistance. Clinical and microbiological data from 293 hospitalized patients with CRKP infections were retrospectively collected at the First Aliated Hospital of Xi’an Jiaotong University from January 2024 to March 2025. Based on CZA susceptibility results, patients were divided into the CZA-sensitive CRKP group (n = 228) and the CZA-resistant CRKP group (n= 64). The colloidal gold detection method was used to identify ve carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and bloat) and their subtypes were determined through PCR application and sanger sequencing. The relative expression of the blaKPC gene was measured using real-time quantitative PCR (RT-qPCR). Multivariate logistic regression analysis was performed to identify risk factors for CZA-resistant CRKP infections. The primary resistance mechanisms for CZA-resistant CRKP in our hospital are the production of metal enzymes, especially KPC-2 and NDM-1 co-producing strains. Some strains exhibit resistance to CZA due to blaKPC-2 mutations and increased gene expression. Multivariate logistic regression analysis revealed that renal replacement therapy and prior CZA exposure were independent risk factors for CZA-resistant CRKP infections.

This study aimed to investigate the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), elucidate the resistance mechanisms to ceftazidime-avibactam (CZA) and identify the risk factors associated with CZA resistance. Clinical and microbiological data from 293 hospitalized patients with CRKP infections were retrospectively collected at the First Aliated Hospital of Xi’an Jiaotong University from January 2024 to March 2025. Based on CZA susceptibility results, patients were divided into the CZA-sensitive CRKP group (n = 228) and the CZA-resistant CRKP group (n= 64). The colloidal gold detection method was used to identify ve carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and bloat) and their subtypes were determined through PCR application and sanger sequencing. The relative expression of the blaKPC gene was measured using real-time quantitative PCR (RT-qPCR). Multivariate logistic regression analysis was performed to identify risk factors for CZA-resistant CRKP infections. The primary resistance mechanisms for CZA-resistant CRKP in our hospital are the production of metal enzymes, especially KPC-2 and NDM-1 co-producing strains. Some strains exhibit resistance to CZA due to blaKPC-2 mutations and increased gene expression. Multivariate logistic regression analysis revealed that renal replacement therapy and prior CZA exposure were independent risk factors for CZA-resistant CRKP infections.

The objective of this review is to analyze the pharmacology, safety, and clinical application of ATM-AVI. PubMed, Embase, and ClinicalTrials.gov were searched using the terms aztreonam avibactam, PF-06947387, Emblaveo, and Aztreonam-avibactam (ATM-AVI). Study selected and data extracted articles written in English and published from Jan 1, 1985, to June 10, 2025, that related to pharmacology, safety, clinical trials, and clinical application of ATM-AVI were reviewed. The ATM-AVI has shown similar efficacy to comparator antibiotics in complicated intra-abdominal infection (cIAI) and hospital/ventilator-acquired pneumonia (HAP/VAP). The REVISIT trial showed cIAI clinical cure rates of 76.4% and 74% for the ATM-AVI and meropenem groups, respectively (treatment difference 2.4% [95% confidence interval, CI = −7.4 to 13.0]). For HAP/VAP, clinical cure rates were 45.9% and 41.7% for the ATM-AVI and meropenem groups, respectively (treatment difference 4.3% [95% CI = −15.1 to 23.1]). The ATM-AVI was generally well tolerated, with hepatic adverse effects being the most commonly reported. The ATM-AVI has demonstrated clinical efficacy for the treatment of cIAI. However, its role needs to be further studied for other infections such as HAP/VAP, urinary tract, and other serious infections.

Relebactam is a new inhibitor of class A and class C β-lactamases. The FDA has approved combining IMI/CS/REL to treat some infectious diseases. This study systematically reviews the efficacy and safety of IMI/CS/REL based on existing clinical trials so as to provide a reference for follow-up research. Researchers comprehensively searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomised controlled trials published up to Mar 28, 2025, with Imipenem/Cilastatin/Relebactam” or “IMI/CS/REL” as keywords and screened the results according to the proposed exclusion and inclusion criteria. The meta-analysis showed no significant differences between IMI/CS/REL and comparators in day 28/30 all-cause mortality, in clinical response rate during the early follow-up period (EFU) and in microbiological response at EFU The adverse events (AEs) rate also showed no statistical difference in each study’s arms. IMI/CS/REL demonstrates a non-inferior efficacy and safety profile compared to standard comparators in treating carbapenem-susceptible or carbapenem-resistant pathogens. Nevertheless, more robust clinical evidence is needed to fully establish its role in real-world practice.

This review provides an updated overview of evolving epidemiological trends of infections caused by New Delhi metallo-β-lactamase (NDM) and OXA-48-producing Enterobacterales, related clinical implications, and both current and emerging treatment options. Ceftazidime/avibactam (CAZ) and aztreonam is the first-line therapeutic option, whereas cefiderocol (CFDC) represents an alternative if susceptibility is confirmed. Resistance to both aztreonam/avibactam and CFDC has been reported among NDM-5–producing E. coli, raising concerns in the scientific community. New agents, including cefepime–zidebactam and cefepime–taniborbactam, are currently in development and may expand the future treatment landscape. For OXA-48–producing CRE, ceftazidime/avibactam and CFDC are currently available therapeutic options, whereas cefepime/enmetazobactam may become available in the next future. Optimal management of NDM- and OXA-48-producing Enterobacterales requires individualized approach guided by pathogen type, resistance profile, and patient characteristics. Improved diagnostics and surveillance are essential to guide early treatment, while novel agents may enhance therapeutic options in the near future.

Eravacycline (ERV), demonstrates broad-spectrum activity against multidrug-resistant (MDR) pathogens. This multicentre retrospective study evaluates the real-world clinical effectiveness of ERV in treating various infections of the patients hospitalized in the respiratory departments. Authors analysed 113 adult patients treated with ERV from respiratory departments in China; ERV exhibited 87.6% clinical efficacy and 85.8% microbiological eradication rate, accompanied by an 85.0% 30-day survival rate. The antibiotic maintained robust activity against MDR pathogens, particularly A. baumannii (n = 51) and K. pneumoniae (n = 27). Adverse events occurred in only 1.8% (2/113) of cases. Clinical outcomes showed no statistically significant differences between monotherapy (n = 70) and combination regimens (n = 43), confirming ERV as an effective and well-tolerated therapeutic option for managing patients in the respiratory departments, particularly those caused by MDR Gram-negative pathogens.

In this study, authors we investigated the prevalence and mechanisms of CZA resistance among CRPA isolates collected from two tertiary hospitals in Hangzhou between 2021 and 2022. A total of 273 non-duplicate CRPA isolates were screened, among which 13.9% (38/273) exhibited CZA resistance (MIC ≥ 16 µg/mL). Whole-genome sequencing revealed that resistant strains were highly resistant to carbapenems, cephalosporins, and aztreonam but retained partial susceptibility to aminoglycosides and polymyxins. KPC-86 was discovered for the first time in P. aeruginosa, embedded in an IS26-flanked transposon, suggesting potential for horizontal transfer. Sequential recovery of KPC-86 and KPC-33 from the same patient supports in vivo evolution under antibiotic pressure. These findings highlight the evolving threat of CZA resistance in CRPA, driven by blaKPC diversification within high-risk clones. Continued genomic surveillance and antimicrobial stewardship are urgently needed to preserve the efficacy of CZA.

A semisynthetic antimicrobial called plazomicin received approval from the US Food and Drug Administration for the treatment of adults with severe complicated urinary tract infections (cUTIs) caused by bacterial pathogens, in cases where the patients have no or limited other therapeutic options. In treating cUTIs, plazomicin has demonstrated that it is comparable to meropenem, and is a practical treatment option for outpatient antibiotic treatment settings (given iv, once daily, with a brief 30 min administration duration). In addition, plazomicin shows low frequency side effects including nephrotoxicity and ototoxicity. Except for the approved use of plazomicin to treat cUTIs, there is a gap in the literature regarding the role of plazomicin in therapy for patients with aggressive and life‑threatening bacterial infections including Enterobacterales. Plazomicin is a reasonably expensive drug that should be used sparingly. In the present review, the molecular characteristics, chemical properties, mechanism of action, antibacterial spectrum, pharmacokinetics, clinical therapeutic indications, side effects, role in therapy and special considerations of plazomicin are discussed.

Intracranial infections caused by carbapenem-resistant K. pneumoniae (CRKP) pose significant therapeutic challenges, primarily due to the limited penetration of antimicrobial agents across the blood-brain barrier. Ceftazidime/avibactam demonstrates efficacy against multidrug-resistant Gram-negative pathogens. However, its CSF pharmacokinetics and optimal dosing in patients with augmented renal clearance remain inadequately characterized. Authors quantified ceftazidime/avibactam concentrations in paired plasma and CSF samples obtained from a traumatic brain injury patient with CRKP ventriculitis and ARC. Standard Ceftazidime/avibactam dosing (2.5 g q8h) resulted in subtherapeutic trough concentrations in both plasma (ceftazidime/avibactam: 10.39/0.96 µg/mL) and CSF (ceftazidime/avibactam: 20.4/0.68 µg/mL) against the target pathogen (MIC = 4 mg/L). Dose intensification to 2.5 g q6h administered via 3-h prolonged infusion achieved supra-therapeutic exposures, which correlated with CSF sterilization and resolution of inflammatory markers. This first-in-human pharmacokinetic evidence in a patient with ARC underscores the inadequacy of conventional ceftazidime/avibactam regimens in this population. Authors findings advocate for therapeutic drug monitoring-guided dose optimization incorporating extended infusions to achieve therapeutic targets.

Carbapenem-resistant K. pneumoniae (CRKP) is a major global health threat, and the emergence of ceftazidime-avibactam (CZA)-resistant KPC variants presents an increasing clinical challenge. This study aimed to investigate the in vivo evolution and phenotypic difference of a KPC-2 variant, KPC-71, during CZA therapy. Seven CRKP isolates were sequentially collected from a single hospitalized patient over a 147-day period. Whole-genome sequencing, phylogenetic analysis, plasmid profiling, antimicrobial susceptibility testing, and virulence assays (including Galleria mellonella infection, siderophore production, and serum resistance) were performed to characterize the evolutionary dynamics and biological consequences of KPC-71, emerged repeatedly during CZA treatment, replacing KPC-2 and conferring high-level CZA resistance while reducing carbapenem MICs. Withdrawal of CZA resulted in reversion to KPC-2, restoring carbapenem resistance and CZA susceptibility, indicating a reversible resistance trade-off. Phylogenetic analysis revealed clonal expansion of the KPC-71-producing sublineage. Plasmid analysis identified blaKPC genes located on a conserved IncFII/IncR-type plasmid containing an intact ISKpn27-blaKPC -ISKpn6 transposon, while progressive remodelling of an IncFII (pCRY) plasmid in CRKP103 led to chromosomal integration of multiple resistance genes. Notably, the final isolate, CRKP103, exhibited markedly reduced capsule production, siderophore activity, serum survival, and attenuated virulence in G. mellonella, which associated with the loss of the iucABCD/iutA locus on an IncHI1B-type virulence plasmid. Functional validation confirmed that KPC-71 expression alone conferred high-level CZA resistance while modulating susceptibility to other β-lactams. This study provides the first clinical evidence of the reversible in vivo evolution of an insertional KPC-71 variant under antibiotic pressure. The findings reveal a dynamic balance between resistance and virulence mediated by blaKPC mutations and plasmid remodelling, highlighting the risk of resistance cycling during CZA treatment and the need for genomic surveillance in managing CRKP infections.

This was a retrospective, single-centre, observational study of 195 adult patients with GNB bacteraemia who received IMI/REL for at least 48 hours. The patient cohort was characterized by a high comorbidity burden and significant illness severity. The most common pathogens were P. aeruginosa (63.1%) and K. pneumoniae (24.6%), with a high proportion of isolates being carbapenem-non-susceptible (77.5%). The primary outcome was clinical success, and secondary outcomes included 30-day all-cause mortality and safety. The overall clinical success rate was 72.82%, and the all-cause 30-day mortality rate was 11.3%. Microbiologic failure occurred in 12.3% of patients, and infection recurrence within 30 days was seen in 8.2%. The safety profile was favourable, with adverse drug reactions reported in 4.1% of patients, leading to treatment discontinuation in only two cases (1.02%). The findings of this study reinforce the value of IMI/REL as an effective and well-tolerated treatment for severe GNB infections in a complex, real-world patient population. These outcomes compare favourably with published data for other new BL/BLI agents, supporting the targeted use of IMI/REL as a crucial component of modern antibiotic stewardship.

This study examines the impact of combining delafloxacin with antibiotics on Pseudomonas aeruginosa (MDR-PA) isolated from various samples. The minimum inhibitory concentrations (MICs) of delafloxacin, alone and in combination with other antibiotics, were determined against forty distinct MDR-PA isolates using the broth microdilution method. Time-kill curve assays were used to determine the bactericidal and synergistic effects of delafloxacin alone and in combination with other antibiotics in vitro against the selected five strains. Authors studies showed delafloxacin exhibited four times greater in-vitro activity against MDR-PA strains than levofloxacin compared with both MIC50 and MIC90 results. Delafloxacin + tobramycin and delafloxacin + ceftazidime/avibactam showed synergy in two out of five strains tested at concentrations equal to the MIC. The outcomes of this research also suggest that these combinations may replace therapy for MDR-PA strains.

The aim of this study was to report three cases of SE or SH infections treated by debridement antibiotic and implant retention (DAIR) surgery and combination of delafloxacin (DFX)/rifampicin. Three patients were involved. Medical characteristic of the patients, the type of surgery, and the bacteria implicated were recovered. Resistance profiles and treatment with the follow up were analysed. Fever was present for 2 patients and fistula for 1. No acute blood-borne infection was reported. The median time between symptom onset and surgical procedure were 5, 22 and 55 days. All strains were considered susceptible and a favourable outcome was noticed for two patients after a one year follow up. However, for the third patient, the one with two S. epidermidis morphotypes, a relapse was observed 1 year after the first revised surgery revealing only the less DFX susceptible SE stain (MIC 0.25 mg/L) suggesting a selection of the strain with the higher DFX MIC leading to a treatment failure. Pulsed-field gel electrophoresis analysis confirmed the genetic link between the isolates. Therefore, DFX treatment can be a therapeutic option in bone and joint infection, even for levofloxacin-resistant strain, only if the DFX MIC is less than 0.094 mg/L .

The study’s aim was to characterize for the first time the intracellular activity of delafloxacin compared to levofloxacin against various serogroups of Legionella pneumophila and species of Legionella in terms of culturability and viability. The infectious capacity of 10 Legionella strains was evaluated individually to ensure a percentage of viable infected macrophage post-infection. Then, the extracellular concentration inhibiting intracellular multiplication (MIEC90), of the antibiotic was determined by gradient antibiotic incubations in the in vitro infection model through culturability assays. Finally, viability of intracellular Legionella was studied by qPCR after antibiotic treatment at MIEC90 value. Delafloxacin decreased the culturability of Legionella from 5 to 10 times more than did levofloxacin. The MIEC90 obtained was 0.025 mg/L for levofloxacin and 0.005 mg/L for delafloxacin for all strains tested except L. longbeachae, the same concentration for both antibiotics was required. The bactericidal effect of both antibiotics was confirmed by viability qPCR. Based on the results obtained, the higher intracellular activity of delafloxacin compared to levofloxacin and its better safety profile should be confirmed in phase IV clinical real-life cases of Legionnaires’ disease.

The aim of this study is to evaluate the pH-dependent antimicrobial activities of delafloxacin against isogenic Escherichia coli strains carrying diverse fluoroquinolone resistance mechanisms. Eighty-one isogenic E. coli strains derived from ATCC 25922 were tested, carrying various combinations of chromosomal mutations (gyrA, parC), efflux pump overexpression (marR), and plasmid-mediated quinolone resistance (PMQR) determinants (qnrA1, qnrB1, qnrC, qnrD1, qnrS1, qepA2, aac(6′)-Ib-cr). Minimum inhibitory concentrations (MICs) were determined using broth microdilution at pH 7.3, 6.0, and 5.0. Time-killing assays were performed on three representative strains. Ciprofloxacin MIC90 increased from 8 mg/L at pH 7.3 to 128 mg/L at pH 5.0, while delafloxacin MIC90 decreased from 64 mg/L to 16 mg/L. At physiological pH, ciprofloxacin demonstrated superior activity (median MIC: 1 mg/L vs 8 mg/L for delafloxacin, P < 0.001), while at pH 5.0, delafloxacin median MIC was 2 mg/L vs 64 mg/L for ciprofloxacin (P < 0.001). According to EUCAST breakpoints, susceptibility frequencies at pH 5.0 were 25.9% (21/81) for delafloxacin vs 2.5% (2/81) for ciprofloxacin (P < 0.001). Simulated clinical exposures against chromosomal mutant EC02 (GyrA-S83L) demonstrated that ciprofloxacin would fail at pH 5.0, while delafloxacin would maintain antimicrobial activity. Environmental pH deeply modulates fluoroquinolone activity and resistance mechanism impact. Delafloxacin demonstrates clinically relevant activity in acidic infection environments.

The aim of this retrospective study is to report the experience with Delafloxacin for the treatment of skin and soft tissue infections in a hospital in São Paulo, as well as to create a database of patients who have used the drug. A total of 36 patients with skin and soft tissue infections were included, assessing clinical and laboratory parameters before and after 72 h of treatment. The results showed significant improvements in laboratory parameters, and the average duration of treatment was 8.7 days, with adverse effects occurring in only 5.5% of patients (delirium and diarrhoea). This study concludes that delafloxacin is an effective and safe therapeutic option, especially in elderly patients with comorbidities, and highlights the need for continuous monitoring given the readmission rate and the complexity of the patients treated. Findings demonstrate significant improvements in inflammatory and renal parameters, a low incidence of adverse events, and a favourable safety profile. Additionally, the analysis of readmission rates offers a more comprehensive assessment of the therapy. The study also highlights delafloxacin’s potential in reducing bacterial resistance, a crucial factor in antibiotic selection.

The objectives of the study were to determine the in vitro activity of delafloxacin in comparison with other fluoroquinolones against clinical isolates of Corynebacterium spp., to compare MICs of delafloxacin obtained with gradient strips and with reference microdilution, and to investigate the mechanisms related to fluoroquinolone resistance in the tested strains. #53 clinical isolates, assigned to five species of Corynebacterium spp., were evaluated using reference microdilution for delafloxacin, ciprofloxacin, levofloxacin, and moxifloxacin (with and without reserpine or phenylalanine-arginine β-naphthylamide), and gradient strips for delafloxacin. The QRDR of the gyrA gene was amplified using primers specific to the different species, and mutations were defined after aligning against the corresponding reference sequences. Delafloxacin was the most active compound with MIC50/MIC90 values of 0.5/8 mg/L. Single mutations at the QRDR were observed in isolates, with MICs of delafloxacin ranging from 0.016 to 4 mg/L, while double mutations occurred in isolates, with MICs ranging from 0.125 to 16 mg/L. The delafloxacin gradient strips showed an essential agreement of 88.7%, bias of −5%, and a Kappa index of 0.848. Increased MICs of delafloxacin against Corynebacterium spp. are related to the presence of non-conservative mutations in the QRDR of gyrA. Delafloxacin could represent an alternative for treating infections due to some species of Corynebacterium.

A Left Ventricular Assist Device (LVAD) utility in heart failure patients is growing. Despite advancement in technology rates of LVAD- related infections remain high limiting outcomes. Authors aimed to assess the effectiveness and safety of oritavancin (ORI) for LVAD-related Gram-positive infections. A retrospective study evaluating adult LVAD patients who received ≥ 1 ORI dose for treatment of Gram-positive LVAD-related infection between September 2022 and December 2024. ORI was given at the end of shortened standard antibiotic therapy. Overall, nine patients were included. Most episodes (80%) were deep drive-line infections. The organism most commonly responsible for infection was S. aureus. ORI was administered after a median time of 31 ± 13 days of standard antibiotic therapy. In total 18 doses of ORI were administered with a median of 2 per case separated on average by 20 ± 4 days. Primary endpoint was achieved in 90% of cases, shortening therapy by a median time of 24 days. Serious adverse events occurred in two of 9 patients: delirium and shivers, both with transient increase of inflammatory markers. ORI has a potential to shorten in hospital therapy and improve outcomes in LVAD-related Gram-positive infections in advanced heart failure patients. This study is the first to report delirium and transient increase in inflammatory biomarkers as side effects.

This was a retrospective observational study evaluating adverse drug reactions (ADRs) associated with oritavancin diphosphate (OD, old formulation) and oritavancin complexed with 2-hydroxypropyl-β-cyclodextrin (OC, new formulation), reported in the U.S. FDA Adverse Event Reporting System (FAERS), with a focus on differences potentially attributable to the HPβCD excipient in the OC formulation, between January 2014 and June 2024. A total of 761 reports were retrieved for OD and 245 for OC. For both formulations, the peak in reporting occurred about 3 years after market introduction. The majority of events were classified as non-serious, accounting for 70.4% of OD and 71.8% of OC cases. Clinical outcomes were largely comparable, though OD showed higher proportions of death (2.2% vs 0.8%), hospitalization (13.2% vs 10.7%), and life-threatening events (3.2% vs 0.8%). Age distribution indicated broader use of OD, including pediatric patients and a higher proportion of adults aged 18 to 64 years, while OC was more frequently reported in elderly patients (65-85 years). Analysis of specific ADRs highlighted distinct patterns: infusion-related reactions, particularly chills, tremors, and flushing, were more frequent with OC, while OD was associated with higher rates of dermatological manifestations such as pruritus, urticaria, rash, and erythema. OC also showed a markedly higher proportion of errors related to multiple use of the single-use vial (9.9% vs 0.8%), whereas off-label use was more common with OD (9.6% vs 4.9%). Although both contain the same active ingredient, OD and OC differ in safety profiles due to their formulation and administration. Both formulations are considered safe, consistent with their product information. These findings highlight the need for formulation-specific safety considerations and standardized protocols in clinical practice.

The clinical landscape of Gram-positive infections has been reshaped with the introduction of long acting lipoglycopeptides, particularly dalbavancin and oritavancin (ORI). Both agents share broad-spectrum activity against multidrug-resistant pathogens, including methicillin-resistant S. aureus and vancomycin-resistant strains, yet differ markedly in pharmacokinetics, pharmacodynamics, resistance profiles, and clinical adoption. This review presents a comprehensive comparative analysis of their structural innovations, distinct pharmacokinetic and pharmacodynamic characteristics, and dual mechanisms of action, supported by minimum inhibitory concentration data across key pathogens. Despite belonging to the same antimicrobial class, these agents exhibit important differences in real-world applications and clinical integration. Authors highlight real-world evidence supporting off-label use in osteomyelitis, endocarditis, and bloodstream infections, where traditional therapies fall short. Furthermore, they explore resistance development, drug–drug interaction profiles, and outpatient utility, providing actionable insights for optimizing treatment strategies. These findings underscore the need for tailored clinical integration of dalbavancin and ORI and spotlight their potential roles in future antimicrobial stewardship frameworks.

The risk of cardiac implantable electronic device (CIED)-related infection in long-term follow-up (F/U) ranges from 1.19% to 3.35%, depending on the type of procedure, the number of implanted electrodes, and patient-related risk factors. Gram-positive cocci are etiological agents of the vast majority of serious CIED infections. The antibiotic of choice for CIED infections caused by multidrug-resistant (MDR) Gram-positive cocci is vancomycin, a first-generation bactericidal glycopeptide antibiotic administered every 8–12 hours under the control of serum concentration. An alternative to vancomycin is the second-generation semisynthetic lipoglycopeptides, including oritavancin (ORI). ORI acts more effectively and faster against Gram-positive cocci than vancomycin. Moreover, ORI has better tissue and intracellular penetration than vancomycin and an excellent potency for eradicating intracellular staphylococcal reservoirs. This pilot study, planned as single center, randomized, non-inferiority controlled trial, will aim to compare the efficacy and safety of two antibiotic dosing regimens in the treatment of CIED-related infections caused by MDR Gram-positive cocci, using a long-half-life lipoglycopeptide antibiotic (ORI) and a short-half-life glycopeptide antibiotic The intervention under investigation (experimental) will involve the administration of a long-half-life lipoglycopeptide antibiotic, oritavancin, as a single dose or as a multiple-dose therapy repeated at 7-day intervals, depending on clinical indication. The active comparator)will be the administration of vancomycin repeated daily in 8- to 12-hour intervals for a period of one to six weeks. The planned recruitment period will last 15 months, followed by a 3-month observation period. The study will be blinded only at the ran­domization stage (open label). The co-primary efficacy endpoint will be the treatment success rate, defined as obtaining a clinical response and no recurrence of infection at the exact location. Once completed, the ORI-4-CIEDi study may be the first RCT to deploy oritavancin in CIED-related infections caused by various types of Gram-positive cocci conducted in a broader group of patients.

This was retrospective observational case series of 10 patients with complicated Gram-positive infections treated with oritavancin (ORI) at a tertiary care centre. Most patients had multiple comorbidities and prior antibiotic toxicities. The primary diagnoses were prosthetic valve endocarditis  (n = 5) and infections of vascular endoprostheses (n = 3). Staphylococcus aureus (n = 3), Staphylococcus epidermidis (n = 3), and Enterococcus faecalis (n = 3) represented the main aetiologias. All patients achieved clinical cure, and no relapses were observed during a follow-up of up to 24 months. ORI was well-tolerated with no reported adverse events. These findings suggest oritavancin may serve as an effective medical alternative to source control in frail, difficult-to-treat populations.

Authors described five cases of PVL-positive CA-MRSA SSTIs admitted to the Infectious Diseases Unit of the University Hospital “Paolo Giaccone,” Palermo, Italy, between 2024 and 2025. Case inclusion followed the CDC criteria for CA-MRSA. Microbiological identification was performed using MALDI-TOF mass spectrometry, and antimicrobial susceptibility testing followed EUCAST standards. PVL gene presence was confirmed by polymerase chain reaction. Clinical management included surgical drainage, systemic antibiotic therapy, and decolonization of both patients and close contacts. Long acting lipoglycopeptides (oritavancin or dalbavancin) were evaluated as therapeutic options to achieve clinical resolution. PVL-positive CA-MRSA infections are characterized by recurrence, intrafamilial clustering, and frequent therapeutic failure with standard oral agents. Effective management requires an integrated approach combining prompt surgical drainage; systemic therapy, preferably including long acting lipoglycopeptides; and comprehensive decolonization of all close contacts.

This pharmacovigilance study analysed Dalbavancin -associated adverse events (AEs) using real-world data from the FDA Adverse Event Reporting System (FAERS) database, addressing the critical need for post-marketing safety surveillance. Using FAERS reports from August 2014 to March 2023 (covering Dalbavancin ’s entire post-marketing period), authors analysed Dalbavancin -associated AEs. Disproportionality analyses employed four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The characteristics of the adverse events were investigated using time-to-onset analysis, the Weibull distribution model, and stratified analysis. A total of 14,787,480 reports listed Dalbavancin as the primary suspect (PS) drug. These yielded 922 Dalbavancin -related AEs comprising 2,257 preferred terms (PTs) across 25 System Organ Classes (SOCs). AE incidence was higher in males (40.56%) than females (35.36%). Most AEs occurred in 2020 (n=133, 14.43%), with serious and non-serious AEs constituting 47.94% and 52.06% of reports. Most AEs occurred within the first treatment month (n=125, 89.29%). Common reactions: rash, pruritus, back pain, erythema, hypersensitivity, vomiting, and urticaria-aligned with prescribing information and clinical trials. Unexpected significant AEs included acute kidney injury, urinary abnormalities, toxic nephropathy, cardiovascular disorders, and sinus tachycardia.

This systematic review and meta-analysis compared the efficacy and safety of LA-LGP to the Standard of Care (SOC) antibiotics for the treatment of these infections. This review conducted using PubMed, Medline, Embase, Cochrane, and Clinicaltrials.gov through November 2024. Prospective and retrospective comparative studies evaluating patients being treated for complicated Gram-positive infections were included. Interventions included multi-dose Long-acting lipoglycopeptides (LA-LGPs), including dalbavancin and oritavancin, vs. SOC antibiotics. Fourteen studies (n = 1582 patients) were included. Studies included a wide array of indications and dosing schemes. LA-LGP was associated with significantly higher clinical success rates compared to SOC. No significant differences were observed for infection recurrence, mortality, adverse events (AEs), or serious adverse events (SAEs). LA-LGP was associated with fewer hospital readmissions. A subgroup analysis of bone and joint infections showed no significant difference in clinical success between LA-LGP and SOC.LA-LGP for the treatment of complicated Gram-positive infections resulted in similar efficacy and safety to SOC antibiotics and may be a reasonable alternative for such infections.

Emerging evidence demonstrates that dalbavancin PK may be significantly altered in obese patients, potentially necessitating adjustments in dosing frequency. However, the therapeutic management of severely underweight patients remains largely unexplored. Authors report the case of a 65-year-old Chinese female patient who required initiation of dalbavancin therapy in November 2024 for infective endocarditis of a biological aortic valve (replaced April 2024) caused by Corynebacterium striatum. She initially received vancomycin, discontinued due to a cutaneous adverse reaction, and was then switched to daptomycin, which was well tolerated. Due to a high surgical risk, the patient was deemed ineligible for repeat cardiac surgery. Following multidisciplinary consultation, a dosing regimen of dalbavancin 1000 mg administered on day 1 and day 8 was initiated. Subsequent dosing intervals were guided based on TDM results, assessing both minimum and maximum dalbavancin plasma concentrations, as previously described. The patient received seven dalbavancin administrations over a 217-day period. Renal and hepatic function remained relatively stable throughout the observation period. In contrast, a progressive increase in body weight was documented, from 28 to 38 kg, paralleling a gradual improvement in inflammatory markers and an overall enhancement of the patient’s clinical condition.