Search Results (94)

Background/Objectives: Antimicrobial resistance (AMR) is considered a major threat by the healthcare community. In this context, the AWaRe (Access, Watch, Reserve) classification of antibiotics is a valuable tool that can assist physicians during the clinical decision process and pharmacists in promoting the rational use of antibiotics. Pharmacovigilance studies based on real-world evidence offer valuable insight into the AMR phenomenon. The aim of this study was the assessment of the resistance, ineffectiveness, and off-label use signals of all five cephalosporins belonging to the Reserve group (ceftazidime/avibactam, ceftaroline, cetolozane/tazobactam, ceftobiprole, and cefiderocol). Methods: The study was conducted using descriptive approaches on EudraVigilance data and disproportionality analyses comparing each of the fourteen cephalosporins in the Watch group. Results: Ceftazidime/avibactam (n = 904, 38.6%) topped the reports, followed by ceftaroline (n = 559, 23.9%) and ceftolazane/tazobactam (n = 560, 23.9%). The lowest number of reports was submitted for cefiderocol (n = 176, 7.5%) and ceftobiprole (n = 146, 6.2%). The resistance to ceftazidime/avibactam, cefiderocol, and ceftolozane/tazobactam was reported with a higher probability than all others, the strongest signal being observed for cefiderocol against cefixime (ROR: 171.25, 95% CI 79.64–368.27). All cephalosporins from the Reserve group (except ceftobiprole) have higher probability for reporting ineffectiveness than cephalosporins from the Watch group; the strongest signal was observed for cefiderocol–cefditoren (ROR: 14.70, 95% CI 6.73–32.11). All cephalosporines from the Reserve group had a higher probability of reporting off-label use by comparison with the ones from the Watch group, except for two cases of no disproportionate signal between cefiderocol–cefoperazone and cefiderocol–ceftizoxime; the strongest signal was observed for ceftolozane/tazobactam–cefotaxim (ROR: 43.61, 95% CI 30.14–63.09). Conclusions: This analysis supplements information from clinical trials and current clinical practice, underscoring the critical need for rigorous antibiotic stewardship programs. Notably, even restricted use of cephalosporins demonstrated therapeutic failure and inappropriate utilization. Full article

Antimicrobial resistance (AMR) continues to represent a significant global public health concern. Gram-negative bacilli (GNB) are the primary causative agents of severe nosocomial infections and possess a notable capacity to develop resistance mechanisms that restrict therapeutic options. The objective of this study was to characterize the antimicrobial susceptibility profiles of GNB isolated at a secondary-level hospital in Guadalajara, Mexico, with the aim of identifying predominant resistance patterns and the most effective therapeutic alternatives. A descriptive, retrospective, cross-sectional study was conducted using clinical isolates of Acinetobacter spp., Pseudomonas spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus spp., and Enterobacter spp. collected during 2024. The identification and susceptibility testing were carried out using the VITEK^® 2 automated system, and the results were interpreted in accordance with CLSI guidelines. High resistance rates were observed in Acinetobacter spp. and Pseudomonas spp., particularly to carbapenems (>50% and >40%, respectively). Escherichia coli and Klebsiella spp. demonstrated resistance to third-generation cephalosporins and trimethoprim/sulfamethoxazole, exhibiting high susceptibility to amikacin and carbapenems (>90%). New-generation β-lactam/β-lactamase inhibitor combinations, such as ceftazidime/avibactam and ceftolozane/tazobactam, have demonstrated high efficacy against resistant strains. Overall, GNB isolates in this secondary-level hospital demonstrated elevated resistance levels, particularly to β-lactams and carbapenems, which pose a significant therapeutic challenge. Nevertheless, amikacin, carbapenems, and new-generation β-lactams persist as valuable therapeutic options. In order to contain the spread of multidrug-resistant organisms, it is imperative to strengthen local surveillance, optimize antibiotic stewardship, and reinforce infection control measures. Full article

Background/Objectives: Therapeutic drug monitoring (TDM) of β-lactams (BL), BL/β-lactamase inhibitor (BLI) combinations (BL/BLIc), and of fosfomycin may play a key role in optimizing antimicrobial therapy and in preventing resistance development, especially when used by continuous infusion in critically ill or immunocompromised patients. Unfortunately, analytical methods for simultaneously quantifying multiple BL/BLIc in plasma are still lacking. Methods: The aim of this study was to develop and validate two rapid, sensitive, and accurate UPLC–qTOF–MS/MS methods for the simultaneous quantification of five novel β-lactam or β-lactam/β-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, cefiderocol, and ceftobiprole) along with fosfomycin. Methods: Human plasma samples were prepared by protein precipitation using methanol containing isotopically labeled internal standards. Chromatographic separation was achieved within 10–12 min using two Agilent Poroshell columns (EC-C18 and PFP) under positive and negative electrospray ionization modes. The method was validated according to the EMA guidelines by assessing selectivity, linearity, precision, accuracy, matrix effects, extraction recovery, and stability. Results: The methods exhibited excellent linearity (R² ≥ 0.998) across the calibration ranges for all of the analytes (1.56–500 µg/mL), with limits of quantification ranging from 1.56 to 15.62 µg/mL. Intra- and inter-day precision and accuracy were always within ±15%. Extraction recovery always exceeded 92%, and the matrix effects were effectively corrected through isotopic internal standards. No carry-over or isobaric interferences were observed. All the analytes were stable for up to five days at 4 °C, but the BL and BL/BLIc stability was affected by multiple freeze–thaw cycles. Conclusions: These UPLC-qTOF-MS/MS multi-analyte methods enabled a simultaneous, reliable quantification in plasma of five novel beta-lactams and of fosfomycin. Robustness, high throughput, and sensitivity make these multi-methods feasible for real-time TDM, supporting personalized antimicrobial dosing and improved therapeutic outcomes in patients with severe or multidrug-resistant infections. Full article

Background: Difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) infections are associated with high morbidity and mortality, but data on prognostic factors remain limited. Given the limited real-world data on outcomes of DTR-PA infections, we aimed to identify clinical predictors of mortality and response to therapy in this setting. Methods: We conducted a single-center retrospective cohort study of 51 patients with DTR-PA infections. The primary endpoint was 30-day all-cause mortality; secondary endpoints were clinical and microbiological cure at end of therapy. An exploratory analysis evaluated 30-day infection-related mortality. Logistic regression models (univariable, multivariable and Firth bias-reduced) were used to identify independent predictors. Results: Median age was 64 years (IQR 22); 63% were male and 71% were in the ICU at infection onset. Sepsis occurred in 80% and septic shock in 45%. Thirty-day all-cause mortality was 49% (25/51). According to multivariable analysis, septic shock was an independent predictor of mortality (aOR 5.52, 95% CI 1.04–29.27; p = 0.045) as younger age (aOR 1.06, 95% CI 1.00–1.12; p = 0.052), whereas targeted therapy with ceftazidime/avibactam or ceftolozane/tazobactam is a protective factor (aOR 0.15, 95% CI 0.02–1.17; p = 0.070) did not reach significance in the final model. Clinical cure occurred in 33% (17/51) and was negatively associated with device burden and bloodstream infection, whereas microbiological cure (45%, 23/51) was more likely with targeted therapy and absence of sepsis. The exploratory analysis of infection-related mortality (35%) showed similar predictors. Conclusions: DTR-PA infections are associated with high mortality. Septic shock and older age predict death, while the use of novel β-lactam/β-lactamase inhibitors is associated with improved outcomes. Early recognition of severe illness and timely administration of active therapy may improve survival in these infections. Full article

Objective: To evaluate the antimicrobial susceptibility of Enterobacterales isolated from pediatric patients. Methods: A total of 5723 isolates were consecutively collected (1/patient) from pediatric patients (<18 years old [yo]) from 82 United States medical centers in 2019–2023 and susceptibility-tested by broth microdilution method. Susceptibility was stratified by infection type and patient age: ≤1 yo (n = 2275), 2–5 yo (n = 1130), 6–12 yo (n = 1213), and 13–17 yo (n = 1105) and compared to adults (18–64 yo; n = 17,712). Results: Pediatric isolates were mainly from pneumonia (21.8%), bloodstream (BSI; 15.3%), and urinary tract infection (UTI; 51.8%). Aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam were active against ≥99.4% of ceftriaxone-nonsusceptible (99.4–100.0% susceptible), multidrug-resistant (MDR; 99.7–100.0% susceptible), and ESBL producer (99.7–100.0% susceptible) isolates from pediatric patients. Susceptibility to imipenem–relebactam varied from 97.1% (ceftriaxone-nonsusceptible) to 100.0% (ESBL producers). Ceftolozane–tazobactam showed good activity against ESBL producers (91.8% susceptible), but limited activity against ceftriaxone-nonsusceptible (75.8% susceptible) and MDR isolates (80.9% susceptible). The MDR phenotype varied from 14.3% (13–17 yo) to 19.7% (6–12 yo) among pediatric isolates (15.8% overall) and was 20.7% among adult Enterobacterales. Carbapenem resistance rates were markedly lower in pediatric (0.1%) isolates compared to adult isolates (1.3%). The ESBL profiles were similar among pediatric and adult isolates; 90.1% of ESBL producers from pediatric patients and 88.5% from adults carried a CTX-M +/− an OXA-1/30 gene. Conclusions: Antimicrobial resistance was generally lower among Enterobacterales from pediatric patients compared to adults. ESBL-producing Enterobacterales, mainly CTX-M, remain an important cause of infection in children. Aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam were highly active against isolates from both pediatric and adult population. Full article

Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane–tazobactam, ceftazidime–avibactam, aztreonam–avibactam, cefiderocol, meropenem–vaborbactam, imipenem–relebactam, and newer agents including sulbactam–durlobactam, cefepime–enmetazobactam, and cefepime–taniborbactam. Pharmacokinetic data, RRT impact, PK/PD targets, pediatric aspects, and clinical outcomes were extracted from experimental models, case reports, and clinical studies. Drug exposure varies with RRT modality, effluent flow, membrane properties, and patient-specific factors such as augmented renal clearance, hypoalbuminemia, and fluid overload. Standard renal-adjusted dosing often yields subtherapeutic concentrations in critically ill patients. Pediatric data remain scarce and largely limited to case reports. Optimal BL/BLI use in septic patients with SA-AKI on RRT requires individualized dosing that accounts for PK/PD variability and dialysis settings. Full-dose initiation during the first 24–48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance. Full article

Objectives: To describe annual trends in the susceptibility of clinical isolates of Pseudomonas aeruginosa from Latin America to ceftolozane/tazobactam. Methods: The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program collected 10,188 P. aeruginosa isolates from 57 unique clinical sites in 12 Latin American countries from 2016 to 2024. MICs were determined by reference broth microdilution testing and interpreted using 2025 CLSI M100 breakpoints. Results: Overall, 86.3% of clinical isolates of P. aeruginosa collected in Latin America were susceptible to ceftolozane/tazobactam, including 45.5% of multidrug-resistant (MDR) isolates. From 2016 to 2024, annual percent susceptible values for ceftolozane/tazobactam ranged from 84.9% (2016, n = 779) to 89.2% (2023, n = 1144), with a statistically significant linear trend for increasing susceptibility (p = 0.024; Cochran–Armitage test for trend). However, limiting analysis solely to the 14 clinical sites, from six countries, that participated in each of the nine years (n = 4565) indicated that the annual percent susceptible values for ceftolozane/tazobactam remained unchanged from 2016 (82.6%) to 2024 (83.9%) (p = 0.367; percent susceptible value range, 82.6 to 89.1%). Every year, from 2016 to 2024, all P. aeruginosa isolates from pediatric patients (<18 years of age) were consistently more susceptible to ceftolozane/tazobactam than those from adult patients (90.3 to 95.0%/year versus 83.3 to 88.6%/year, respectively). Significant variation (p < 0.05) in annual ceftolozane/tazobactam percent susceptible values was not observed for isolates from blood, intra-abdominal, and respiratory tract sources, while isolates from urine showed a trend of increasing ceftolozane/tazobactam susceptibility from 73.1% (2018, n = 145) to 90.6% (2023, n = 117) (p < 0.0001). Among individual countries that participated each year, P. aeruginosa isolates from all except Guatemala displayed stable or increasing rates of susceptibility to ceftolozane/tazobactam. Conclusions: Since it was first tested by the SMART program in 2016, and for 8 years thereafter, the in vitro activity of ceftolozane/tazobactam has remained consistent against clinical isolates of P. aeruginosa from the Latin American region (overall, 86.3% susceptible), with limited resistance development restricted to specific clinical sites. Full article

Introduction: Antimicrobial resistance is a significant public health issue worldwide, associated with limited treatment options and with major consequences for healthcare systems. Our study aims to assess rates and patterns of resistance to five last-resort antimicrobials in a cohort of carbapenemase-producing Klebsiella pneumoniae strains, isolated over a one-year interval. Additionally, we have tested two potentially synergistic combinations for in vitro efficacy. Methods: This prospective observational study evaluated Klebsiella pneumoniae strains with diminished carbapenem susceptibility from patients admitted to the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in Bucharest between August 2023 and July 2024. Strains presenting a minimum inhibitory concentration to meropenem of >0.125 μg/mL underwent phenotypic enzyme production testing, followed by synergistic testing to identify antimicrobial salvage therapy options. A subset of these strains was analysed for the detection of plasmid-mediated resistance genes, using a custom workflow for DNA extraction and amplification/detection. Results: A total of 139 non-duplicate strains were isolated, with 129 (92.8%) being carbapenemase producers. These 129 strains were phenotypically diverse: 29 (22.5%) were NDM, 12 (9.3%) OXA-48 type, 8 (6.2%) KPC, while most of them (62.0%) were double carbapenemase producers: 79 (61.2%) NDM and OXA-48-type, and one strain was NDM and KPC. Forty-six strains were resistant to cefiderocol (35.7%), 108 (83.7%) to ceftazidime/avibactam, 127 (98.4%) to ceftolozane/tazobactam, 116 (90.0%) to imipenem/relebactam and 127 (98.4%) to aztreonam. The association of aztreonam with ceftazidime/avibactam demonstrated a synergistic effect in 127 (98.5%) strains, while aztreonam with imipenem/relebactam was efficient in vitro against 103 (79.8%) strains. Conclusions: Antimicrobial resistance remains a concerning phenomenon among Enterobacterales, especially when considering the increasing resistance rates even against salvage therapy antimicrobials. Full article

Background/Objectives: Parenteral antibiotic therapy is indispensable in the treatment of several infections. The parenteral administration often leads to the need for prolonged hospitalization. Therefore, interest in outpatient parenteral antimicrobial therapy (OPAT) is growing. OPAT is typically administered in elastomeric devices, which release an infusion solution over a 24 h period and are meanwhile worn close to the body. This work aimed to evaluate the stability of the reserve antibiotics ceftazidime-avibactam and ceftolozane-tazobactam for OPAT use. Methods: Elastomeric pumps were prepared in triplicate at the dosages 3.75 and 7.5 g of ceftazidime-avibactam and 2.25, 4.5, and 9.0 g of ceftolozane-tazobactam in 240 mL 0.9% saline each. The pumps were first stored at 2–8 °C for 7 days and subsequently incubated for 48 h at 25 °C. To determine actual concentrations of ceftazidime, avibactam, ceftolozane, tazobactam, and pyridine, samples were taken at nine different time points during storage and incubation. High-performance liquid chromatography coupled to tandem mass spectrometry was used for quantification. Results: Although concentrations of ceftazidime and avibactam stayed above 90% during a 24 h incubation period at 25 °C, the pyridine limit of the European Pharmacopeia was already exceeded in the ceftazidime-avibactam pumps after the storage time at 2–8 °C. In the ceftolozane-tazobactam pumps, the ceftolozane concentration was stable for 24 h incubation, but tazobactam concentrations decreased below 90% within 12 h in the two higher dosages. Conclusions: Accordingly, stability cannot be guaranteed for both tested preparations and their use for OPAT should be thoroughly considered. Full article

Background/objectives: Proteus mirabilis is a frequent causative agent of urinary and wound infections in both community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESCs) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpCs). Recently, carbapenem-resistant isolates of P. mirabilis emerged due to the production of carbapenemases, mostly belonging to Ambler classes B and D. Here, we report an outbreak of infections due to carbapenem-resistant P. mirabilis that were observed in a psychiatric hospital in Zagreb, Croatia. The characteristics of ESBL and carbapenemase-producing P. mirabilis isolates, associated with an outbreak, were analyzed. Materials and methods: The antibiotic susceptibility testing was performed by the disk-diffusion and broth dilution methods. The double-disk synergy test (DDST) and inhibitor-based test with clavulanic and phenylboronic acid were applied to screen for ESBLs and p-AmpCs, respectively. Carbapenemases were screened by the modified Hodge test (MHT), while carbapenem hydrolysis was investigated by the carbapenem inactivation method (CIM) and EDTA-carbapenem-inactivation method (eCIM). The nature of the ESBLs, carbapenemases, and fluoroquinolone-resistance determinants was investigated by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). Selected isolates were subjected to molecular characterization of the resistome by an Inter-Array Genotyping Kit CarbaResisit and whole-genome sequencing (WGS). Results: In total, 20 isolates were collected and analyzed. All isolates exhibited resistance to amoxicillin alone and when combined with clavulanic acid, cefuroxime, cefotaxime, ceftriaxone, cefepime, imipenem, ceftazidime–avibactam, ceftolozane–tazobactam, gentamicin, amikacin, and ciprofloxacin. There was uniform susceptibility to ertapenem, meropenem, and cefiderocol. The DDST and combined disk test with clavulanic acid were positive, indicating the production of an ESBL. The MHT was negative in all except one isolate, while the CIM showed moderate sensitivity, but only with imipenem as the indicator disk. Furthermore, eCIM tested positive in all of the CIM-positive isolates, consistent with a metallo-β-lactamase (MBL). PCR and sequencing of the selected amplicons identified VIM-1 and VIM-4. The Inter-Array Genotyping Kit CarbaResist and WGS identified β-lactam resistance genes bla_VIM, bla_CTX-M-15, and bla_TEM genes; aminoglycoside resistance genes aac(3)-IId, aph(6)-Id, aph(3″)-Ib, aadA1, armA, and aac(6′)-IIc; as well as resistance genes for sulphonamides sul1 and sul2, trimethoprim dfr1, chloramphenicol cat, and tetracycline tet(J). Conclusions: This study revealed an epidemic spread of carbapenemase-producing P. mirabilis in two wards in a psychiatric hospital. Due to the extensively resistant phenotype (XDR), therapeutic options were limited. This is the first report of carbapenemase-producing P. mirabilis in Croatia. Full article

Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are challenging multidrug-resistant pathogens. This study evaluated the in vitro susceptibility of CRE and CRPA blood isolates from Korea to novel β-lactam/β-lactamase inhibitor combinations: ceftolozane/tazobactam (C/T), ceftazidime/avibactam (CZA), imipenem/cilastatin/relebactam (IMR), and meropenem/vaborbactam (MEV). Methods: Blood isolates of CRE (n = 55) and CRPA (n = 65) collected between September 2017 and September 2022 in a Korean tertiary hospital were included. Carbapenemase production was determined using phenotypic and molecular methods. In vitro susceptibility to C/T, CZA, IMR, and MEV was determined primarily by broth microdilution using current CLSI/EUCAST breakpoints. Clinical characteristics and in-hospital mortality were retrospectively reviewed. Results: Among non-carbapenemase-producing (non-CP) CRPA isolates (n = 47), susceptibility rates were 83.0% to C/T and 70.2% to CZA. For KPC-producing CRE isolates (n = 28), susceptibility rates were high to CZA (92.9%), IMR (82.1%), and MEV (96.4%). However, non-CP CRE isolates (n = 22) showed low susceptibility to C/T (18.2%) but high susceptibility to CZA (100%), IMR (81.8%), and MEV (95.5%). CRE infections were associated with higher rates of hematologic malignancy, immunosuppression, and in-hospital mortality (63.6% vs. 18.5% for CRPA, p < 0.001). Conclusions: The susceptibility of CRE and CRPA to novel β-lactam/β-lactamase inhibitors varies significantly by species and carbapenemase production. CZA, IMR, and MEV showed promising activity against KPC-producing CRE. These findings can inform empirical therapy and stewardship efforts in Korea. Full article

Neonatal sepsis is a major cause of morbidity and mortality in neonates. A particular concern is the increasing prevalence of antibiotic-resistant strains among neonatal intensive care units (NICUs). Two novel beta-lactam/beta-lactamase inhibitors have recently been approved for use in neonates with multidrug-resistant infections: ceftazidime/avibactam and ceftolozane/tazobactam. These agents demonstrate efficacy against a range of multidrug-resistant gram-negative pathogens, including extended-spectrum beta-lactamases (ESBL)-producing and carbapenem-resistant Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa. This narrative review aims to summarize the current knowledge concerning the utilization of ceftazidime/avibactam and ceftolozane/tazobactam in the NICU. According to the existing literature, both agents have been shown to be highly effective with a favorable safety profile in the neonatal population. Full article

Respiratory tract infections are frequently encountered in clinical practice. The growing incidence of antimicrobial resistance among the causative pathogens exerts sustained pressure on the existing therapeutic options. The emergence of antimicrobial resistance limits the treatment options and often leads to unfavorable patient outcomes. However, in the past few years, newly developed antibiotics have become available, providing viable choices for antibiotic-resistant infections. New β-lactam/β-lactamase combinations, such as ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam, are effective against carbapenem-resistant Enterobacterales. Several new drugs including ceftolozane/tazobactam are active against multi-drug-resistant Pseudomonas aeruginosa, while sulbactam/durlobactam and cefiderocol have potent activity against Acinetobacter baumannii. A number of new options, such as lefamulin, omadacycline, and delafloxacin, have also emerged for pathogens commonly associated with community acquired pneumonia. This article aims to review the characteristics of newly approved antibiotics for the treatment of respiratory tract infections, as well as to discuss some investigational agents that are currently under development. Full article

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections present a significant clinical challenge due to limited therapeutic options and high transmission potential. This study aimed to identify the resistance genes associated with carbapenemase production in CRKP isolates and evaluate the in vitro activity of ceftazidime/avibactam (CZA) and meropenem/vaborbactam (MEV), among other β-lactam/β-lactamase inhibitor combinations. Methods: Between October 2021 and June 2022, a total of 504 CRKP isolates were grown from patient samples in intensive care units. When duplicate patient samples were removed, the remaining 89 isolates were included in the study. Bacterial identification and antimicrobial susceptibility testing were per-formed using MALDI-TOF, Phoenix M50, and disk diffusion methods, following EUCAST guidelines. PCR analyses identified carbapenemase genes such as OXA-48, NDM, and KPC. Results: The most prevalent carbapenemase gene was OXA-48 (79.8%), followed by NDM (21.4%) and KPC (17.9%). The susceptibility rate to CZA was 82.0%, significantly higher than MEV (10.1%). All isolates were resistant to piperacillin/tazobactam and ceftolozane/tazobactam. Among MEV-resistant isolates, most carried the OXA-48 gene, while NDM was common in CZA-resistant isolates. Conclusions: CZA demonstrates high efficacy against OXA-48-producing CRKP, making it a viable treatment option in settings where OXA-48 predominates. The limited activity of MEV in this study underscores the need for molecular surveillance of resistance mechanisms to guide empirical therapy. Full article

The management of infections caused by difficult-to-treat Pseudomonas aeruginosa in critically ill patients poses a significant challenge. Optimal antibiotic therapy is crucial for patient prognosis, yet the numerous resistance mechanisms of P. aeruginosa, which may even combine, complicate the selection of an appropriate antibiotic. In this review, we examine the epidemiology, resistance mechanisms, risk factors, and available and future therapeutic options, as well as strategies for treatment optimization. Finally, we propose a treatment algorithm to facilitate decision making based on the resistance patterns specific to each Intensive Care Unit. Full article