Meropenem-vaborbactam (MVB) and ceftazidime-avibactam (CAZ-AVI) are active against “urgent threat” pathogens like carbapenem-resistant Enterobacterales (CRE). However, few studies have compared outcomes between them. A multicenter retrospective cohort study of all adult hospitalized patients with a serious infection (sepsis, urinary tract infection complicated intraabdominal infection, or pneumonia) within the PINC AI Database, 2019-2021 was conducted to explore comparative outcomes of MVB vs. CAZ-AVI. Descriptive statistics compared the two groups along demographic and clinical characteristics, and multiple regression derived adjusted outcomes. Among 1,989,765 patients who met enrollment criteria, 455 received MVB and 2320 CAZ-AVI. Their mean [SD] Charlson comorbidity scores did not differ (3.6 [2.5] vs. 3.5 [2.5], p = 0.403). The most common index infection in both groups was pneumonia, though it was less prevalent in the MVB – than the CAZ-AVI-treated group (48.1% vs. 56.8%, p = 0.001). Fewer than one-third of all patients received the respective drug within 2 days of the onset of the index infection (30.6% MVB vs. 33.0% CAZ-AVI, p = 0.313). Fewer patients on MVB than CAZ-AVI required mechanical ventilation (35.0% vs. 41.4%, p = 0.010). MVB treatment was associated with lower adjusted mortality (17.0% [95% CI 13.6%, 20.3%] vs. 20.6% [95% CI 19.0%, 22.2%], p = 0.048) relative to CAZ-AVI. In this cohort of hospitalized patients treated with either MEV or CAZ-AVI for their infectious syndrome, MVB was associated with lower adjusted hospital mortality, although the confidence intervals around the values overlapped.

This prospective observational study evaluated the epidemiology, management, microbiological characterization, and outcomes of hospital-acquired CRE or CRPA infections treated in selected ICUs in Italy. The study included patients with hospital-acquired infections due to CRE and CRPA treated in 20 ICUs from June 2021 to February 2023. The primary endpoint was the 1-year incidence of CRE/CRPA infections. Among 13,088 patients admitted over the 12-month study period across each of the 20 ICUs, 283 had CRE infections, and 138 had CRPA infections. The incidence of CRE and CRPA infections was 3.57 per 1000 patient days and 1.74 per 1000 patient days, respectively. Among the 94 CRE isolates, the most common species was Klebsiella pneumoniae (n = 87, 92.5%). In this group, 77 KPC-producing Enterobacterales were isolated, 100% of them were susceptible to aztreonam-avibactam (AZA), IMI-REL and MVB, 94% to FDC and 86% to CAZ-AVI. The proportion of CRE and CRPA infections over the total number of infections due to Enterobacterales and Pseudomonas aeruginosa was 19.2% and 26.8%, respectively. The overall crude mortality in ICU rate was 30.4%, with a higher rate in CRE patients (36.7%) than in CRPA patients (20.0%). Clinical success, including microbiological eradication, was achieved in 50.6% of cases.

To evaluate the in vitro activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparators against KPC-producing Klebsiella pneumoniae (KPC-Kp) clinical isolates were collected from a multicentre study in Italy (2022-23) and genomic characterization of the molecular mechanisms causing resistance. Consecutive KPC-Kp isolates from blood cultures (n = 264) were collected from 14 hospital centres in the period 2022-23. Overall, meropenem/vaborbactam (95.1% susceptible by EUCAST and 93.9% susceptible by CLSI; MIC50 = 0.5 mg/L; MIC90 = 4 mg/L) and imipenem/relebactam (97% susceptible by EUCAST and 92.8% susceptible by CLSI; MIC50 = 0.25 mg/L; MIC90 = 0.5 mg/L) showed similar activity, followed by ceftazidime/avibactam (93.9% susceptible by both EUCAST and CLSI; MIC50 = 2 mg/L; MIC90 = 8 mg/L). Ten out of 13 (76.9%) KPC-Kp resistant to ceftazidime/avibactam carried a blaKPC variant including blaKPC-31, blaKPC-205, blaKPC-203 and blaKPC-93. Among KPC-Kp resistant to meropenem/vaborbactam and imipenem/relebactam, 90.9% (10/11) and 80% (4/5) harboured a WT carbapenemase (i.e. blaKPC-2 or blaKPC-3), respectively. All strains resistant to meropenem/vaborbactam and/or imipenem/relebactam carried truncated OmpK35 and/or mutated (ins135GD) OmpK36.

This multicentre, retrospective, observational study was conducted at 28 hospitals in the USA between Jan 1, 2016, and Dec 31, 2023. Eligible patients were adults (age ≥18 years old) with microbiologically confirmed multidrug-resistant P aeruginosa pneumonia or bacteraemia treated with ceftolozane–tazobactam or ceftazidime–avibactam for more than 48 h. Patients were matched (1:1) by study site, severity of illness, time to treatment initiation (≤72 h or >72 h), and infection type. The primary outcome was clinical success at day 30, which was defined as survival, resolution of signs and symptoms of infection with the intended treatment course, and the absence of recurrent infection due to P. aeruginosa. Secondary outcomes included all-cause mortality and development of resistance to study drug. 420 eligible patients were included (210 in each treatment group), of whom 350 (83%) had pneumonia and 70 (17%) had bacteraemia. Baseline demographics, comorbidities, and severity of illness indicators were similar between groups. On treatment initiation, 336 (80%) patients were in the intensive care unit, 296 (70%) were receiving mechanical ventilation, and 168 (40%) required vasopressor support. Clinical success was observed in 128 (61%) of 210 patients treated with ceftolozane–tazobactam and 109 (52%) of 210 patients treated with ceftazidime–avibactam. For patients with pneumonia, clinical success was observed in 110 (63%) of 175 patients in the ceftolozane–tazobactam group and 89 (51%) of 175 patients in the ceftazidime–avibactam group. Among patients with bacteraemia, rates of clinical success were 51% (18 of 35 patients) for patients treated with ceftolozane–tazobactam and 57% (20 of 35 patients) for those treated with ceftazidime–avibactam. There were no significant differences between groups in 30-day or 90-day mortality. Among patients whose baseline isolates were tested for susceptibility, resistance developed in 22% (38 of 173) of patients treated with ceftolozane–tazobactam and 23% (40 of 177) of patients treated with ceftazidime–avibactam. Treatment with ceftolozane–tazobactam resulted in higher rates of clinical success compared with ceftazidime–avibactam for invasive infections due to multidrug-resistant P aeruginosa. Differences were driven by improved response rates for patients with pneumonia who were treated with ceftolozane–tazobactam. There were no significant differences between study groups with respect to all-cause mortality; treatment-emergent resistance was common with both agents.

Metallo-β-lactamases (MBLs) in Enterobacterales and other Gram-negative organisms pose significant public health threats due to their association with multidrug resistance (MDR). Although aztreonam (AZT) can target MBL-producing organisms, its efficacy is compromised in organisms expressing additional β-lactamases that inactivate it. Combining AZT with the β-lactamase inhibitor avibactam (AVI) may restore its activity against MBL-producing isolates. AZT-AVI, along with other clinically relevant antimicrobials, was tested against thirteen MBL-producing clinical isolates of Enterobacterales (nine Klebsiella pneumoniae, three Enterobacter cloacae, and one Providencia stuartii) using whole-genome sequencing (WGS) for genetic characterization. AZT-AVI demonstrated full susceptibility across all isolates, whereas aztreonam alone was ineffective. The newer β-lactam/β-lactamase inhibitor combinations imipenem/relebactam and meropenem/vaborbactam were inactive in 100% and 92.3% of isolates, respectively. WGS-based analysis revealed multiple resistance mechanisms consistent with MDR phenotypes, including high-risk K. pneumoniae clones (ST147 and ST11). AZT-AVI is effective against MDR MBL-producing Enterobacterales, highlighting its therapeutic potential for challenging infections. While WGS does not replace phenotypic testing, it provides valuable insights for antimicrobial stewardship and the monitoring of resistance gene dissemination.

in vitro synergistic effect of the CAZ-AVI/ATM combination. The study included 48 CRKP strains isolated from various clinical samples. Identification was performed using MALDI-TOF MS (bioMérieux, France), and susceptibility was tested with Vitek-2 (bioMérieux). The susceptibility to CAZ-AVI and ATM was determined using CAZ-AVI 30/20 µg and ATM 30 µg (Oxoid™,UK) disks. Carbapenemase genes VIM, NDM, IMP, KPC, OXA-23, OXA-58, OXA-48, and OXA-51 were investigated in only 44 isolates using the Bio-Speedy Carbapenem resistance qPCR (Bioexen, Turkiye) kit. Synergy testing was evaluated with double disk diffusion, gradient strip (bioMérieux)/disk diffusion, and broth disk elution methods. Out of 48 carbapenem-resistant isolates, 40 (83.3%) isolates showed resistance to CAZ-AVI and 46 (95.8%) to aztreonam. Synergy was detected with all three methods in all isolates identified as resistant to CAZ-AVI, CAZ-AVI-sensitive isolates were not included in this evaluation. The most frequently detected carbapenemase genes were NDM+OXA-48, found in 28 (63.6%) of the isolates. Although the NDM+OXA-48 coexistence predominates in our center, in vitro synergy between CAZ-AVI and ATM was detected in all of CAZ-AVI-resistant isolates. Performing the CAZ-AVI+ATM synergy test and reporting the result is crucial for choosing appropriate treatment in CRKP infection.

Currently, new β-lactam/β-lactamase inhibitor (BL/BLI) combinations, such as ceftazidime–avibactam (CAZ-AVI), imipenem–relebactam and meropenem–vaborbactam and cefiderocol (CFDC) have been recommended as the first choice of therapy for infections caused by CR-GNB. These combinations are active against class A (KPC) and class C β-lactamases (AmpC) but have no activity against metallo-β-lactamases (MBL); CAZ-AVI is also active on OXA-48 producing Enterobacterales and P.aeruginosa isolates, whereas, CFDC demonstrates promising in vitro activity against all clinically important carbapenemases including MBL. In recent years, studies have shown that K. pneumoniae, the most common carbapenem-resistant organism in this country, carries both types of NDM with the same OXA-48 gene. Therefore, given the prevalence of carbapenemase genes in Iran, aztreonam plus CAZ-AVI would find greater utility and CAZ-AVI should not be prescribed experimentally and as monotherapy. Recently, the first report of failure of ceftazidime/avibactam experimental therapy in a 91-year-old man with K. pneumoniae ST11 co-producing NDM-1 and OXA-48 carbapenemases infection was reported in Iran. It should be noted that in an ongoing study, the results show that out of 78 carbapenem-resistant K. pneumoniae isolated from patients in two medical centers in Isfahan, 87.2% are resistant to CAZ-AVI due to NDM production in approximately 50% of cases. These results confirm that CAZ-AVI as monotherapy is not a suitable treatment choice for patients. The indiscriminate and experimental use of CAZ-AVI without proper diagnostic support has led to a cascade of detrimental consequences.

Prospective observational multicenter study including patients with bacteremic nosocomial pneumonia(NP) caused by GNB from the ALARICO Network (June 2018-January 2020). The primary outcome measure was 30-day mortality and a Cox regression analysis was performed to identify factors independently associated with 30-day mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated. 167 patients total with GNB NP were included: 101 with bacteremic NP caused by CR-GNB (n = 39 by KPC-producing K.pneumoniae, n = 29 by carbapenem-resistant A. baumannii, n = 28 by carbapenem-resistant P. aeruginosa, n = 5 by MBL-producing K. pneumoniae) and 66 cases of bacteremic CS-GNB NP. Thirty-day mortality rate was higher in patients with NP caused by CR-GNB compared to those with NP caused by CS-GNB. On multivariable analysis, age, hematological malignancy and septic shock were factors independently associated with 30-day mortality, while the receipt of adequate antibiotic therapy within 24 h from infection onset was a protective factor. Carbapenem resistance was not associated with increased risk of mortality. Patients with bacteremic NP caused by CR-GNB have high mortality rate. Strategies to reduce the time from infection to the administration of adequate antibiotic therapy should be implemented in patients with NP.

This systematic review and metanalysis of 11 studies (5 RCTs and 7 observational studies) was conducted to assess the efficacy and safety of cefiderocol (CFDC) in the treatment of Gram-negative bacteria (GNB) infections. After a comprehensive study selection, 11 studies (5 RCTs and 7 observational studies) were retrieved that compared the efficacy of CFDC with other regimens, e.g., imipenem/cilastatin. The clinical response (RR = 1.00, 95% CI 0.94-1.08, I2 = 0%) and microbiological response (RR = 0.95 95% CI = 0.80-1.14, I2 = 68.7%) of CFDC were comparable to the control group. No significant differences were observed in mortality and adverse events.

This study evaluated the in vitro activity of anti-pseudomonal β-lactam molecules combined with recently developed and commercially available β-lactamase inhibitors, such as avibactam, relebactam and vaborbactam, against P. aeruginosa isolates overproducing their AmpC by evaluating the MIC values ​​of these antibiotics with or without β-lactamase inhibitor determined for 50 clinical isolates of P. aeruginosa overproducing AmpC. The MIC breakpoints for resistance were maintained at 8 mg/L for β-lactam and β-lactam/β-lactamase inhibitor combinations containing ceftazidime, cefepime and meropenem, while 4 mg/L was used for those containing imipenem and ceftolozane. The concentration of all β-lactamase inhibitors was set at 4 mg/L, except for vaborbactam (8 mg/L). The results of the study showed that all combinations, including relebactam, produced higher rates of “non-resistance” against clinical isolates of P. aeruginosa that overproduced AmpC. The best activity was obtained by combining ceftolozane and relebactam, which could therefore be considered an excellent clinical alternative against overproducers of AmpC.

Authors developed delafloxacin (Dela)-loaded PLGA nanoparticles (PNPs) for potential ocular application via a topical route to treat eye infections caused by Gram-positive and Gram-negative bacteria. Dela-PNPs were formulated using the emulsification-solvent evaporation method and stabilized using poly (vinyl alcohol) (PVA). Drug loading and encapsulation efficiency were measured via HPLC. Differentials canning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) assessed the physical state and drug−polymer inter action. The in vitro drug release was evaluated using the dialysis bag method in simulated tear fluid (STF, pH 7.4) with Tween 80 (0.5%). The antimicrobial efficacy was determined by a minimum inhibitory concentration (MIC) and zone of inhibition tests against various bacteria. Optimally sized PNPs were produced with a PDI of 0.258 ± 0.084 and a ζ-potential of 2.78 ± 0.34 mV. Using 40 mg of PLGA, 4 mg of Dela, and 1% PVA, drug encapsulation and loading were 84.6 ± 7.3 and12.9 ± 1.7%, respectively. DSC indicated that Dela was entrapped in an amorphous state within the PNPs. The formulation showed 40.6 ± 4.2% drug release within 24 h and 84.4 ± 6.1% by 96 h. MIC tests showed high susceptibility of S. pneumoniae, K. pneumoniae, and E. coli (∼0.31 μg/mL) compared to S. aureus and MRSA-6538 (∼0.63 μg/mL) and B. subtilis (2.5 μg/mL). Stability studies showed minimal changes in particle characteristics over 3- and 6-month storage at 25 and 37 °C. Dela-PNPs exhibit significant potential as a nano-formulation for ocular applications.

Kimyrsa, also known by its generic name, oritavancin, is a potent, long-acting antibiotic typically prescribed for the treatment of bacterial skin infections in adults. This antibacterial medication is classified as a glycopeptide antibiotic. It is effective against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, and Enterococcus faecalis. Kimyrsa was first approved by the U.S. Food and Drug Administration in August 2014 for the treatment of bacterial skin infections. It is given as a single, one-hour IV infusion. This reduces the need for long hospital stays or repeated doses compared to other antibiotics, such as vancomycin.

The aim of the study was to describe the clinical effectiveness of DAL in the treatment of ABSSSI, with or without concomitant osteoarticular infections (OAIs), in obese patients compared with non-obese patients. Over a three-year period, hospitalized subjects with ABSSSI who were treated with DAL were included. Patients were further divided into two groups according to the presence/absence of obesity (BMI ≥ 30 kg/m²). Furthermore, obese patients treated with DAL were compared with obese patients treated with SOC (1:1 ratio). Overall, 45 subjects treated with DAL (12 obese and 33 non-obese) and 8 obese subjects treated with SOC regimens (1:1 ratio) were included. Obese patients treated with DAL had a similar clinical resolution to non-obese patients. However, obese patients tended to have a better cure rate in ABSSSI than OAI. The subgroup of obese patients with ABSSSI had a high clinical resolution, which was comparable to that of SOC. DAL was overall highly tolerated in obese patients. In this real-world study, DAL confirmed its high effectiveness in the treatment of ABSSSI, including in a difficult-to-treat population such as obese patients