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Abstract Background The SENTRY Antimicrobial Surveillance Program was established in 1997 and encompasses over 750 000 bacterial isolates from ≥400 medical centers worldwide. Among the pathogens tested, Pseudomonas aeruginosa remains a common cause of multidrug-resistant (MDR) bloodstream infections and pneumonia in hospitalized patients. In the present study, we reviewed geographic and temporal trends in resistant phenotypes of P. aeruginosa over 20 years of the SENTRY Program. Methods From 1997 to 2016, 52 022 clinically significant consecutive isolates were submitted from ≥200 medical centers representing the Asia-Pacific region, Europe, Latin America, and North America. Only 1 isolate per patient per infection episode was submitted. Isolates were identified by standard algorithms and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry. Susceptibility testing was performed by Clinical and Laboratory Standards Institute (CLSI) methods and interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing 2018 criteria at JMI Laboratories. Results The most common infection from which P. aeruginosa was isolated was pneumonia in hospitalized patients (44.6%) followed by bloodstream infection (27.9%), with pneumonia having a slightly higher rate of MDR (27.7%) than bloodstream infections (23.7%). The region with the highest percentage of MDR phenotypes was Latin America (41.1%), followed by Europe (28.4%). The MDR rates were highest in 2005–2008 and have decreased in the most recent period. Colistin was the most active drug tested (99.4% susceptible), followed by amikacin (90.5% susceptible). Conclusions Over the 20 years of SENTRY Program surveillance, the rate of MDR P. aeruginosa infections has decreased, particularly in Latin America. Whether the trend of decreasing resistance in P. aeruginosa is maintained will be documented in future SENTRY Program and other surveillance reports.

We evaluated the in vitro activity of ceftibuten-avibactam against Enterobacterales causing urinary tract infection (UTI). A total of 3216 isolates (1/patient) were consecutively collected from patients with UTI in 72 hospitals from 25 countries in 2021 then susceptibility tested by CLSI broth microdilution. Ceftibuten-susceptible breakpoints currently published by EUCAST (≤ 1 mg/L) and CLSI (≤ 8 mg/L) were applied to ceftibuten-avibactam for comparison. The most active agents were ceftibuten-avibactam (98.4%/99.6% inhibited at ≤ 1/ ≤ 8 mg/L), ceftazidime-avibactam (99.6% susceptible [S]), amikacin (99.1%S), and meropenem (98.2%S). Ceftibuten-avibactam (MIC 50/90 , 0.03/0.06 mg/L) was fourfold more potent than ceftazidime-avibactam (MIC 50/90 , 0.12/0.25 mg/L) based on MIC 50/90 values. The most active oral agents were ceftibuten (89.3%S; 79.5% inhibited at ≤ 1 mg/L), levofloxacin (75.4%S), and trimethoprim-sulfamethoxazole (TMP-SMX; 73.4%S). Ceftibuten-avibactam inhibited 97.6% of isolates with an extended-spectrum β-lactamase phenotype, 92.1% of multidrug-resistant isolates, and 73.7% of carbapenem-resistant Enterobacterales (CRE) at ≤ 1 mg/L. The second most active oral agent against CRE was TMP-SMX (24.6%S). Ceftazidime-avibactam was active against 77.2% of CRE isolates. In conclusion, ceftibuten-avibactam was highly active against a large collection of contemporary Enterobacterales isolated from patients with UTI and exhibited a similar spectrum to ceftazidime-avibactam. Ceftibuten-avibactam may represent a valuable option for oral treatment of UTI caused by multidrug-resistant Enterobacterales.

Surfactants might impact treatment of lower respiratory tract infections. Moreover, other body fluids, such as urine or serum, could impact antibacterial activity as well. Therefore, the impact of surfactants, urine, and serum on the antibacterial activity of the novel β-lactam/β-lactamase inhibitor combination of cefepime-enmetazobactam (FPE) was determined. Ten clinical isolates of Klebsiella pneumoniae, and the quality control strains K. pneumoniae ATCC 700603 and Escherichia coli NCTC 13353, were tested. Minimal Inhibitory Concentration (MIC) determinations (all strains) and Time Kill Curves (TKC) (one clinical isolate) were determined for FPE and piperacillin-tazobactam (TZP) with and without surfactant formulations Survanta® (SUR; 1%v/v) and Curosurf® (CUR; 1 mg ml−1). Determination of daptomycin MIC against Staphylococcus aureus ATCC 29213 in the presence and absence of surfactants was used as a positive control. Additionally, the impact of growth media supplemented with pooled human urine or serum were also evaluated by MIC testing. Expectedly, media supplemented with SUR increased the daptomycin MIC against S. aureus ATCC 29213. In contrast, the surfactants had no impact on the antibacterial activity of FPE against the tested Enterobacterales isolates. TKC experiments also revealed no impact of CUR on the antibacterial activity of FPE. These results demonstrate that the antibacterial activity of FPE is unaffected in the presence of lung surfactant. Moreover, FPE was not impacted by media supplemented with urine or serum.

Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017–2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC50/90, 2/>8 mg/L) inhibited 59.6% and 71.2% of all Mucorales isolates at ≤2 mg/L and ≤4 mg/L, respectively. Among comparators, amphotericin B (MIC50/90, 0.5/1 mg/L) displayed the highest activity, followed by posaconazole (MIC50/90, 0.5/8 mg/L). Voriconazole (MIC50/90, >8/>8 mg/L) and the echinocandins (MIC50/90, >4/>4 mg/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at ≤4 mg/L 85.2%, 72.7%, and 25% of Rhizopus spp. (n = 27; MIC50/90, 1/>8 mg/L), Lichtheimia spp. (n = 11; MIC50/90, 4/8 mg/L), and Mucor spp. (n = 8; MIC50, >8 mg/L) isolates, respectively. Posaconazole MIC50/90 values against Rhizopus, Lichtheimia, and Mucor species were 0.5/8 mg/L, 0.5/1 mg/L, and 2/- mg/L, respectively; amphotericin B MIC50/90 values were 1/1 mg/L, 0.5/1 mg/L, and 0.5/- mg/L, respectively. As susceptibility profiles varied among Mucorales genera, species identification and antifungal susceptibility testing are advised whenever possible to manage and monitor mucormycosis.

Dalbavancin and comparators were susceptibility tested against 8643 Gram-positive bacteria from 74 hospitals located in Europe and the United States by broth microdilution method. The most common organisms were Staphylococcus aureus (45.2%), Enterococcus faecalis (12.2%), and Staphylococcus epidermidis (8.9%), but rank order varied markedly by geographic region. Dalbavancin demonstrated potent activity and broad spectrum, with MIC 90 values of 0.03 mg/L for Staphylococcus aureus , β-haemolytic streptococci, and viridans group streptococci; 0.06 mg/L for Enterococcus faecalis and Staphylococcus epidermidis ; and 0.12 mg/L for vancomycin-susceptible Enterococcus faecium . All organisms, except vancomycin-resistant enterococci and 1 Staphylococcus haemolyticus isolate, were inhibited at ≤ 0.25 mg/L of dalbavancin.

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC 90 ) of 0.03–2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias. In this work, the authors probe the efficacy of BWC0977, a bacterial topoisomerase inhibitor, in pre-clinical animal models, also demonstrating that BWC0977 is safe and well tolerated in healthy human volunteers, in a phase 1 trial.

Abstract Streptococcus pneumoniae isolates from the United States (n = 1038; 2019–2021) were susceptible to omadacycline (99.8%), levofloxacin (99.7%), and ceftriaxone (98.1%), whereas doxycycline (80.2%), oral penicillin (63.5%), cefpodoxime (76.8%), and azithromycin (54.4%) activity was limited. Tet(M) did not affect omadacycline activity but altered activity of older tetracyclines including doxycycline, suggesting omadacycline is an important option for treatment of community-acquired bacterial pneumonia.

We report a multicity outbreak of cfr-containing linezolid-resistant Staphylococcus epidermidis in Ohio. Thirty-nine isolates were obtained from 2 hospitals. Two clones with different mechanisms of linezolid resistance were circulating in hospital A. One of these contained the cfr gene, and the other a ribosomal mutation. The clone containing cfr was identical in both hospitals.