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.

Lefamulin, a new, first-in-class pleuromutilin antibiotic, was recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of patients with community-acquired bacterial pneumonia (CABP). In this context, this review aimed to evaluate its activity against the most common pathogens causing this infection. A thorough search was performed in five databases (Embase, Scopus, Web of Science, PubMed, PubMed Central) from their inception to 14th of October 2025. Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints were applied. Out of a total of 224 articles identified, 11 were deemed eligible for inclusion. Resistance among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus isolates was 0–2.6%, 0–2.4%, and 0–4.3%, respectively. Even among isolates with specific mechanisms of resistance, such as β-lactamase-producing H. influenzae and methicillin-resistant S. aureus, resistance was below 2.4% and 3.4%, respectively. Among isolates for which no breakpoints were available (Moraxella catarrhalis, atypical pathogens, Enterococcus spp., Streptococcus spp., Haemophilus spp., and Staphylococcus spp.), MIC₉₀ values were low. An exception were isolates belonging to Enterococcus spp., which displayed MIC₉₀ values ranging from 0.25 to >16 mg/L in the two studies with relevant data. Lefamulin demonstrated broad in vitro activity against key pathogens causing CABP, making it a considerable addition to the therapeutic options for such infections, especially in cases where first-line agents cannot be used for reasons such as allergy or previous failure.