Klebsiella pneumoniae carbapenemases (KPCs) are a group of class A β-lactamases of Gram-negative bacteria leading to difficult-to-treat infections. We evaluated the global epidemiology of KPC-producing Gram-negative clinical isolates. A systematic search of six databases (Cochrane Library, Embase, Google Scholar, PubMed, Scopus, and Web of Science) was conducted. Extracted data were tabulated and evaluated. After screening 1993 articles, 119 were included in the study. The included studies originated from Asia (n = 49), Europe (n = 29), North America (n = 14), South America (n = 11), and Africa (n = 3); 13 studies were multicontinental. The most commonly reported KPC-producing species were Klebsiella pneumoniae (96 studies) and Escherichia coli (52 studies), followed by Enterobacter cloacae (31), Citrobacter spp. (24), Klebsiella oxytoca (23), Serratia spp. (15), Enterobacter spp. (15), Acinetobacter baumannii complex (13), Providencia spp. (11), Morganella spp. (11), Klebsiella aerogenes (9), Pseudomonas aeruginosa (8), Raoultella spp. (8), Proteus spp. (8), and Enterobacter aerogenes (6). Among the studies with specific bla_KPC gene detection, 52/57 (91%) reported the isolation of bla_KPC-2 and 26/57 (46%) reported bla_KPC-3. The antimicrobial resistance of the studied KPC-producing isolates was the lowest for ceftazidime–avibactam (0–4%). Resistance to polymyxins, tigecycline, and trimethoprim–sulfamethoxazole in the evaluated studies was 4–80%, 0–73%, and 5.6–100%, respectively. Conclusions: The findings presented in this work indicate that KPC-producing Gram-negative bacteria have spread globally across all continents. Implementing proper infection control measures, antimicrobial stewardship programs, and enhanced surveillance is crucial.

Introduction: Eravacycline is a new fluorocycline antibiotic with a broad spectrum of antimicrobial activity approved for the treatment of patients with complicated intra-abdominal infections. This systematic review aimed to evaluate the published data on the resistance of Gram-negative bacterial isolates to eravacycline. Methods: We identified relevant publications by systematically searching Embase, PubMed, Scopus, and Web of Science from their inception to 29 August 2025. Published antimicrobial resistance breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the US Food and Drug Administration (FDA) were used. Results: Data on 59,922 Gram-negative bacterial clinical isolates were retrieved from 68 articles after the screening of 283 potentially relevant studies. The resistance of consecutive (non-selected) Escherichia coli ranged from 0.9% to 9.6%. The MIC₅₀ values of eravacycline were ≤0.5 mg/L for Acinetobacter baumannii isolates, including carbapenem-resistant A. baumannii, in the majority of studies. The proportions of resistance were higher among other lactose non-fermenting Gram-negative bacterial isolates, especially Pseudomonas aeruginosa, as well as among selected E. coli with advanced patterns of antimicrobial resistance. Conclusions: The evaluated data support the adequate antimicrobial activity of eravacycline against most Gram-negative bacterial clinical isolates. However, in vitro antimicrobial susceptibility testing and modern molecular diagnostic tests, including those that examine mechanisms of resistance, are helpful for the appropriate use of eravacycline in clinical practice.

This systematic review assessed the global epidemiology of metallo-β-lactamase (MBL)-producing Acinetobacter clinical isolates and the associated antimicrobial resistance. A total of 475 relevant articles from the Cochrane Library, Google Scholar, PubMed, Scopus, and Web of Science were identified and screened as potentially eligible articles. Data from 85 articles were extracted for the analysis. Most reports on MBL-producing Acinetobacter clinical isolates originated from Asia [68/85 (80%) studies] and Africa [14/85 (16.5%) studies]. There were also scarce reports from Europe and America. The bla_VIM (in 31 studies), bla_IMP (in 29 studies), and bla_NDM (in 21 studies) genes were the most commonly identified genes. In 22 out of 28 (78.6%) studies with comparable data, the proportions of MBL-producing pathogens detected using phenotypic methods were numerically higher than those using genotypic methods. MBL-producing Acinetobacter isolates showed high resistance (up to 100%) to several antibiotic classes, including carbapenems, cephalosporins, fluoroquinolones, and monobactams. However, they showed low resistance to colistin [ranging from 0% (in six studies) to 14.3% (in one study)] and to tigecycline [0% (in three studies)]. No risk of bias assessment was conducted. The findings emphasize the global spread of MBL-producing Acinetobacter and the need for enhanced antimicrobial stewardship, infection control measures, and surveillance.

Cefepime-enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination showing good activity against multidrug-resistant (MDR) Gram-negative bacteria producing a variety of β-lactamases. In this systematic review, we aimed to evaluate the available data on resistance to this drug. We performed a thorough search of four databases (Embase, PubMed, Scopus, and Web of Science), as well as backward citation searching, to identify studies containing data on resistance to cefepime-enmetazobactam. The data were extracted and analyzed according to the breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA), or the specific breakpoints reported by the authors of the respective studies. Analysis based on the type of lactamases produced by the isolates was also performed. Ten studies reported in vitro susceptibility testing and mechanisms of antimicrobial resistance. The total number of isolates was 15,408. The activity of cefepime-enmetazobactam against β-lactamase-producing isolates was variable. The resistance of the studied extended-spectrum β-lactamase (ESBL)-producing and ampicillin C β-lactamase (AmpC)-producing isolates was low (0–2.8% and 0%, respectively). The resistance was higher among oxacillinase-48 β-lactamase (OXA-48)-producing and Klebsiella pneumoniae carbapenemase (KPC)-producing isolates (3.4–13.2% and 36.7–57.8%, respectively). High resistance was noted among metallo-β-^lactamase (MBL)-producing isolates (reaching 87.5% in one study), especially those producing New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM), which had the highest rates of resistance. The high activity of cefepime-enmetazobactam against Enterobacterales and selected lactose non-fermenting Gram-negative pathogens, including ESBL-producing and AmpC-producing isolates, makes it a potential carbapenem-sparing agent. The drug should be used after in vitro antimicrobial susceptibility testing in patients with infections caused by OXA-48, KPC, and MBL-producing isolates.

Background: The increasing worldwide problem of bacterial infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens has led to consideration of intravenous fosfomycin, especially in combination antimicrobial regimens. We performed a systematic review of the evidence from comparative and non-comparative studies of patients who received intravenous fosfomycin as monotherapy or in combination with other antibiotics. Methods: Relevant studies were sought in six resources (Cochrane Library, Google Scholar, PubMed Central, PubMed, Scopus, and Web of Science) and two registries [ClinicalTrials.gov and International Clinical Trials Registry Portal (ICTRP)]. Results: Of the 2351 screened articles, 53 (31 comparative and 22 non-comparative studies) reported relevant data for patients with infections at various sites caused by Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, and Gram-positive bacteria, including Staphylococcus spp. and enterococci. Intravenous fosfomycin, either as monotherapy or combination therapy, showed similar or, in some studies, better efficacy (clinical and microbiological cure) compared to therapy with antimicrobial agents not including fosfomycin. The data evaluated also suggest that intravenous fosfomycin has a good safety profile. The administration of the antibiotic may be associated with electrolyte imbalances, especially hypokalemia and hypernatremia. These adverse events may be prevented and controlled with appropriate therapeutic measures and rarely lead to the discontinuation of the drug. Conclusions: Overall, the considerable body of published data suggests that intravenous fosfomycin is safe and effective. The antibiotic may be considered for patients with both Gram-positive and Gram-negative infections, especially in critically ill patients and/or deep-seated infections. The heterogeneity of the included studies is a limitation that prevents firm conclusions.

Infections caused by MBL-producing Gram-negative bacterial pathogens have disseminated worldwide and are associated with considerable morbidity and mortality. We evaluated the published clinical evidence on the use of various antibiotics for the treatment of patients with such infections. The available data suggest the consideration of the new antibiotics cefiderocol and aztreonam-avibactam for the treatment of patients with infections caused by MBL-producing Gram-negative bacterial pathogens. However, their considerable cost and limited availability hinder their use. Also, the combination of ceftazidime-avibactam and aztreonam has been occasionally used, especially when there was an unavailability of aztreonam-avibactam. Additionally, old antibiotics such as colistin and fosfomycin, especially in combination antimicrobial therapy, may be considered for the treatment of patients with such infections. The relevant clinical data on the use of tigecycline and aminoglycosides for infections caused by MBL-producing pathogens are limited. Thus, the evaluation of the published evidence suggests the best treatment options for the treatment of patients with such infections at present. Also, the limited available data highlight the need for dissemination of the already acquired clinical experience and the conduct of new studies examining currently available antibiotics, as well as investigational antimicrobial agents for the treatment of patients with infections caused by MBL-producing Gram-negative bacterial pathogens.