This paper emphasizes that real-world evidence (RWE) plays a critical role in addressing clinical gaps left by pivotal randomized trials, helping to define the optimal place in therapy and dosing regimens for novel anti-MDR Gram-negative agents. By implementing well-designed pathogen-driven and PK/PD studies, RWE can maximize clinical effectiveness in special populations while minimizing the risk of resistance development. For example, for meropenem-vaborbactam the real-world evidence confirmed clinical effectiveness in large cohorts of patients having KPC-producing Enterobacterales infections. Moreover, in real world prolonged/continuous infusion was reported as optimal strategy for maximizing aggressive PK/PD target attainment in most cases, thus minimizing the risk of microbiological failure and resistance occurrence. For this agent, a potential future application of RWE could be to define optimal dosing regimens in critically ill or in haematological patients. Ultimately, an integrated collaboration among researchers, clinicians, and regulators is essential to promptly incorporate these real-world findings into updated clinical guidelines and regulatory decisions.

CRE bacteremia occurred in 12.4% of all CRE-positive cases, a proportion that has increased over time. 30-day mortality was 34.1%; qSOFA, septic shock were independent predictors. Carbapenemase production and combination therapy did not independently predict mortality. Mortality benefit was observed in patients receiving definite colistin-based combination. Amikacin and colistin retained high activity against KPC-producing K. pneumoniae

This retrospective cohort study found that ceftazidime/avibactam (CAZ/AVI)-based therapy was associated with significantly higher clinical response, better microbiological eradication, and lower sepsis-related mortality compared to colistin–meropenem in liver transplant recipients. However, 30-day all-cause mortality did not differ between the treatment arms, and the authors note that these observational findings require prospective validation due to limited economic and appropriateness data.

This study analyzed 33 cases of post-neurosurgical carbapenem-resistant Klebsiella pneumoniae CNS infections, focusing on antimicrobial therapy, therapeutic drug monitoring (TDM), and source control. Successful management primarily involved definitive source control, susceptibility-guided systemic and local antimicrobial therapy optimized by TDM, and delayed VPS placement when necessary. Although infection control was achieved in 97% of cases, neurological outcomes remained poor in 39% of the overall cohort, highlighting the challenge of achieving functional recovery.

Aztreonam-avibactam was tested against 12,039 Enterobacterales from Asia and Latin America during a 5-year period prior to its approval. Aztreonam-avibactam was active against 99.9% of Enterobacterales and 97.3% of CRE. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam showed limited activity against CRE isolates. Metallo-β-lactamases prevailed in Asia and KPCs predominated in Latin America, but with great variability among countries.

Resistance to ceftazidime/avibactam and meropenem/vaborbactam is increasing among carbapenem-resistant Enterobacterales in US hospitals, partly due to the growing prevalence of metallo-β-lactamase producers. Aztreonam/avibactam showed potent activity, inhibiting over 90% of isolates resistant to these treatments and approximately 98% of both CRE and MBL-producing isolates. Other β-lactamase inhibitor combinations and cefiderocol were less effective, highlighting aztreonam/avibactam as a promising therapeutic option.

This study evaluated a rapid enrichment-PCR assay targeting 16 common bloodstream infection pathogens, achieving 97.48% concordance with conventional diagnostic methods and providing results within 2 hours.
In 50 patients with suspected BSI, direct whole-blood testing identified all 14 culture-confirmed infections and six additional culture-negative infections validated by mNGS, reducing the median time to pathogen identification from 19.6 to approximately 4 hours. The assay also improved sensitivity tenfold and enabled targeted antimicrobial adjustments in five of the six additional cases, suggesting potential for faster BSI diagnosis and earlier treatment optimization, although larger studies are needed for validation.

Ceftazidime-avibactam vs. BAT: higher cure for CR-GNB infections in 59 Chinese adults. Favorable microbiological response for ceftazidime-avibactam vs. BAT. Ceftazidime-avibactam vs. BAT: comparable all-cause mortality and well-tolerated. Ceftazidime-avibactam is effective & safe in Chinese adults with CR-GNB infections.

This study evaluated the use of WHO Reserve antibiotics in a tertiary paediatric hospital, analysing 96 treatment episodes in 76 mostly highly comorbid patients, with bloodstream infections being the most common indication. Cefiderocol and ceftazidime–avibactam were generally prescribed according to resistance and microbiological criteria, whereas ceftolozane–tazobactam and ceftaroline were more often used empirically. The implementation of antimicrobial stewardship measures, including formulary restriction and indication-based prescribing tools, provided a practical framework to improve the appropriate use of these last-resort antibiotics.

This review evaluates the pharmacology and clinical utility of tebipenem pivoxil (UTEBZI), the first oral carbapenem approved by the US FDA in June 2026 for selected adults with complicated urinary tract infections (cUTIs). Phase 3 trials demonstrated that oral tebipenem is noninferior to intravenous carbapenems, retaining activity against ESBL- and AmpC-producing Enterobacterales while lacking reliable efficacy against carbapenemases. Ultimately, the authors conclude that tebipenem is an important culture-directed option to replace continuation of IV therapy, though its clinical implementation requires careful stewardship oversight, susceptibility confirmation, and further research on switch strategies.

This study evaluated the efficacy of delafloxacin against 117 Staphylococcus aureus isolates, demonstrating high susceptibility rates among skin and soft tissue infections as well as blood cultures. Based on these findings and the diverse clonal profiles confirmed by FTIR spectroscopy, the authors conclude that delafloxacin represents a strong therapeutic option for managing both MSSA and MRSA infections.

This computational docking and molecular dynamics simulation study identified delafloxacin as the quinolone antibiotic with the highest binding affinity against wild-type Mycobacterium tuberculosis DNA gyrase. Analyzing structural dynamics and geometric changes caused by the A90V and A90E mutations clarifies delafloxacin resistance mechanisms, providing computational insights that assist in developing novel antibiotics with enhanced efficacy, aiding in the development of more effective future antibiotics.

An in-silico PK/PD study evaluated oritavancin 1,200 mg administered weekly or every 2 weeks for prolonged treatment of Gram-positive infections. A six-dose weekly regimen was predicted to maintain free plasma concentrations above the susceptibility breakpoint (0.12 µg/mL) for a median of 10.4 weeks, compared with 8.4 weeks for three doses administered every 2 weeks. Both regimens were predicted to maintain therapeutic concentrations between doses, suggesting that biweekly administration may offer a more convenient and potentially cost-saving strategy. However, these simulation-based findings require clinical validation to establish optimal multidose regimens.

Long-acting antibiotics are agents designed to maintain stable therapeutic concentration over extended periods while reducing dose frequency, thereby optimizing healthcare logistics and facilitation the transition to outpatients’ care. The need for such alternatives is particularly critical in paediatric populations. This article critically reviews the available scientific evidence on the use, dosing and clinical efficacy of dalbavancin and oritavancin in the paediatric population.

Single-dose antibiotics offer opportunities to optimize care for select patients with skin and soft tissue infections. There are 2 long-acting lipoglycopeptides available in the United States, dalbavancin and oritavancin, which have broad gram-positive activity and significantly long half-lives, allowing for single-dose therapy. Both have been shown to be noninferior to standard of care antibiotics when administered as a single dose. These drugs can prevent patients from requiring hospitalization for intravenous antibiotics or expedite discharge for those already admitted. They also have a role in patients with barriers to succeeding with oral antibiotics due to adherence challenges or contraindications.

Skin and soft tissue infections (SSTI) range from mild cellulitis to life-threatening necrotizing fasciitis and are commonly caused by beta-haemolytic streptococci or Staphylococcus aureus. Diagnosis is mainly clinical, although point-of-care ultrasound can help distinguish cellulitis from an abscess, and treatment generally involves antibiotics for cellulitis and incision and drainage for abscesses. Most patients can be discharged with follow-up, while those with sepsis, immunosuppression, poor treatment adherence, or failed outpatient therapy should be referred to the emergency department.

The Canadian CLEAR registry evaluated 160 patients treated with dalbavancin, primarily for acute bacterial skin and skin-structure infections (55.6%) and bone/joint infections (24.4%). MRSA was the most frequently treated pathogen (55.6%), while dalbavancin was mainly administered as monotherapy (83.1%), often as a single 1,500 mg dose (63.0%). Among patients with available outcomes, clinical success was 86.4% (89/103) and microbiological success 93.8% (106/113), with only one adverse event reported. These findings support dalbavancin as a potentially useful option for selected Gram-positive infections, particularly when simplified administration or earlier hospital discharge is desirable.