Zemdri (plazomicin) / Ionis, Achaogen - LARVOL DELTA

Plazomicin: A promising novel antimicrobial in the era of bacterial resistance (Review). (PubMed, Exp Ther Med) - "In treating cUTIs, plazomicin has demonstrated that it is comparable to meropenem, and is a practical treatment option for outpatient antibiotic treatment settings (given intravenously, once daily, with a brief 30 min administration duration). Plazomicin is a reasonably expensive drug that should be used sparingly. In the present review, the molecular characteristics, chemical properties, mechanism of action, antibacterial spectrum, pharmacokinetics, clinical therapeutic indications, side effects, role in therapy and special considerations of plazomicin are discussed."

Journal • Review • Infectious Disease • Nephrology

Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus. (PubMed, J Antimicrob Chemother) - "Apramycin exhibits more potent in vitro activity against a diverse set of M. abscessus and other rapidly growing mycobacteria than currently recommended aminoglycosides."

Journal • Infectious Disease • Nontuberculous Mycobacterial Disease • Otorhinolaryngology

Plazomicin Pharmacokinetics in Indian Complicated Urinary Tract Infections Patients: A Subgroup Analysis From Phase 2 Study. (PubMed, Clin Pharmacol Drug Dev) - "Dose-normalized AUC0-24 and Cmax point estimates were 110% and 103%, respectively. This showed comparable plazomicin exposure in Indian and non-Indian patients."

Journal • P2 data • PK/PD data • Infectious Disease • Nephrology

The novel plasmid pCF1 can be acquired by sensitive Pseudomonas aeruginosa in the lungs of people with CF and cause extreme tobramycin resistance (NACFC 2025) - "This gene also produced resistance to kanamycin and gentamicin; but neither the aac(3)-like gene nor aph(3)-Ib gene conferred resistance to amikacin, netilmicin, apramycin, and plazomicin. The novel pCF1 plasmid encodes a novel aminoglycoside N-acetyltransferase that produces eTobR and can be transferred to sensitive Pa strains from other organisms within the lungs of PwCF. The plasmid produces minimal fitness costs to host Pa and is highly stable even in the absence of antibiotics. These characteristics make pCF1 acquisition a particular threat to the health of PwCF."

Infectious Disease

Synergistic action between peptide-neomycin conjugates and polymyxin B against multidrug-resistant gram-negative pathogens. (PubMed, Front Microbiol) - "The combination of aminoglycosides and colistin is often used to treat pneumonia caused by multidrug-resistant bacteria...Most A. baumannii strains are resistant to amikacin, gentamicin, tobramycin, and plazomicin, and approximately half are susceptible to neomycin...Resistance to the combination of R-, C-, or RC-NEO conjugates and PB did not develop over a 14-day period in neomycin-susceptible strains of A. baumannii, K. pneumoniae, and P. aeruginosa. Based on this survey of the peptide-neomycin library, circumvention of aminoglycoside-modifying enzymes and alluding to bacterial resistance is an important step toward the design and development of peptide aminoglycoside-based motifs for antimicrobial drug development."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Performance evaluation of plazomicin susceptibility testing of Enterobacterales on VITEK 2 and VITEK 2 Compact Systems. (PubMed, J Clin Microbiol) - "There are three species, Klebsiella pneumoniae, Escherichia coli, and Serratia marcescens, for which the trend is ≥ 30% and therefore addressed as a note in the US label. The plazomicin test met the ISO and FDA criteria of ≥95% reproducibility and ≥95% quality control (QC) results within acceptable ranges for QC organisms.IMPORTANCEThe VITEK 2 AST-GN plazomicin test is a new, automated alternative to the BMD reference method for determining minimum inhibitory concentrations (MIC) of Enterobacterales, expanding the range of automatic AST testing."

Journal • Infectious Disease • Pneumonia

Nephrotoxicity of New Antibiotics: A Systematic Review. (PubMed, Toxics) - "The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and sulbactam/durlobactam. There is a need for post-marketing studies to better characterize renal safety. Clinicians should remain vigilant and continue to monitor for and report renal-related adverse events."

Journal • Review

Meropenem/Vaborbactam Combinations with Aminoglycosides Overcome KPC-Producing Klebsiella pneumoniae (ASM Microbe 2025) - "M/V, gentamicin (GENT) and plazomicin (PLZ) pharmacokinetic profiles that approximated antibiotic exposures in the ELF were used. GENT and PLZ displayed limited activity as monotherapy against susceptible KPC-Kp isolates. M/V alone was bactericidal, but resistance emerged during treatment. Combining an AMG with M/V enhanced bacterial killing and protected against the emergence of resistance."

Infectious Disease • Pneumonia • Respiratory Diseases

Meropenem/Vaborbactam Combinations with Aminoglycosides Overcome KPC-Producing Klebsiella pneumoniae (ASM Microbe 2025) - "M/V, gentamicin (GENT) and plazomicin (PLZ) pharmacokinetic profiles that approximated antibiotic exposures in the ELF were used. GENT and PLZ displayed limited activity as monotherapy against susceptible KPC-Kp isolates. M/V alone was bactericidal, but resistance emerged during treatment. Combining an AMG with M/V enhanced bacterial killing and protected against the emergence of resistance."

Infectious Disease • Pneumonia • Respiratory Diseases

Enhanced Activity of Apramycin and Apramycin-Based Combinations Against Mycobacteroides abscessus. (PubMed, bioRxiv) - "The goal of this study was to compare apramycin's in vitro activity with amikacin and other aminoglycosides against a large collection of M. abscessus clinical isolates, both alone and in combination with clofazimine or linezolid...Plazomicin was inactive, and organisms were rarely susceptible to tobramycin...Apramycin was similarly potent against other rapidly growing mycobacteria tested. Apramycin exhibits more potent in vitro activity against a diverse set of M. abscessus and other rapidly growing mycobacteria than approved aminoglycosides."

Journal • Infectious Disease • Nontuberculous Mycobacterial Disease • Otorhinolaryngology • Respiratory Diseases

Efficacy and Safety of Antimicrobial Medications in Treating Infections Caused by Extended-Spectrum; -Lactamase-Producing Enterobacteriaceae: A Systematic Review and Network Meta-analysis (ISPOR 2025) - "In these pairwise comparisons, Sitafloxacin and Ceftolozane-tazobactam showed the best clinical outcomes in comparison to piperacillin-tazobactam, while Plazomicin excelled in microbiological cure. However, Ertapenem and Cefepime were associated with higher ADRs and mortality, respectively.Keywords: Network meta-analysis, Extended-Spectrum β-Lactamase, Enterobacteriaceae, Efficacy and Safety"

Retrospective data • Review • Infectious Disease

The newly identified grdA gene confers high-level plazomicin resistance in Salmonella enterica serovars. (PubMed, Antimicrob Agents Chemother) - "Here, we report that Salmonella enterica strains containing the newly identified gentamicin resistance gene (grdA) are highly resistant to plazomicin. Heterologous expression of grdA in Escherichia coli ΔtolC resulted in plazomicin resistance with minimum inhibitory concentration (MIC) > 256 µg/mL. These findings reveal that GrdA confers significantly higher resistance to plazomicin than the previously known plazomicin-resistant AMEs AA (2)-Ia and APH (2″)-Iva."

Journal • Infectious Disease • Nephrology

Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms. (PubMed, Arch Microbiol) - "Porin modifications reduce the influx of antibiotics, whereas overexpression of efflux pumps, particularly those in the resistance-nodulation-cell division (RND) family, actively expels antibiotics from bacterial cells, significantly lowering intracellular drug concentrations and leading to treatment failure.This review examines the mechanisms of action, resistance profiles, and pharmacokinetic/pharmacodynamic characteristics of newly developed antibiotics designed to combat infections caused by MDR and carbapenem-resistant Gram-negative pathogens. The antibiotics discussed include ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, meropenem-vaborbactam, aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline."

Journal • Review • Critical care • Infectious Disease

Comparative phenotypic and genotypic antimicrobial susceptibility surveillance in Achromobacter spp. through whole genome sequencing. (PubMed, Microbiol Spectr) - "Newer agents like delafloxacin, plazomicin, and omadacycline showed little or no activity, while minimum inhibitory concentrations were low for eravacycline. In general, the species other than A. xylosoxidans showed lower MIC50 and MIC90, especially to carbapenems and β-lactamase inhibitor combinations like piperacillin-tazobactam, meropenem-vaborbactam, and imipenem-relebactam...Our study provides phenotypic data regarding identification and susceptibility testing and correlates this with the genotypic characterization of 109 clinical isolates belonging to Achromobacter spp. This comprehensive study sheds light on the phenotypic and genotypic character of this bacteria, that is of increasing clinical relevance in hospital-acquired infections."

Journal • Infectious Disease

Efficacy of treatment options for complicated urinary tract infections including acute pyelonephritis: a systematic literature review and network meta-analysis. (PubMed, J Comp Eff Res) - "For composite outcome at test of cure (TOC), ceftolozane + tazobactam, cefepime + enmetazobactam, cefiderocol, levofloxacin and plazomicin demonstrated significantly higher RRs versus carbapenems. For microbiological eradication at TOC, cefepime + enmetazobactam, plazomicin, cefiderocol, fosfomycin, meropenem + vaborbactam and ceftazidime + avibactam demonstrated significantly higher RRs versus carbapenems. RRs for cefepime + enmetazobactam were also significantly higher versus several established and novel treatment options for composite outcome, microbiological eradication and clinical cure. Against the backdrop of increasing bacterial resistance, these findings suggest that cefepime + enmetazobactam may represent an effective carbapenem-sparing treatment option in patients with cUTI including AP."

Journal • Retrospective data • Infectious Disease • Nephrology

A systematic review of efficacy and safety of newer drugs approved from 2016 to 2023 for the treatment of complicated urinary tract infections. (PubMed, Ann Med) - " Among the drugs used for treating complicated urinary tract infections, meropenem had the highest cure rate at 91.4%, followed by plazomicin at 88% and cefiderocol at 73% when used as monotherapy. In combination therapy, meropenem-vaborbactam had the highest cure rate at 98.4%, followed by piperacillin-tazobactam at 94%, and ceftazidime-avibactam at 87.5%. The safety profiles of the drugs indicated that almost all drugs caused gastrointestinal symptoms, with imipenem-relebactam and colistin-imipenem combinations having the most serious adverse events. Cefiderocol had a low magnitude of adverse events, with most side effects being mild gastrointestinal symptoms. The study concludes that appropriate drug selection and treatment adherence are crucial for preventing complicated urinary tract infections and improving health outcomes."

Journal • Review • Gastrointestinal Disorder • Infectious Disease • Nephrology • Transplantation

NpmC, a novel A1408 16S rRNA methyltransferase in the gut of humans and animals. (PubMed, Int J Antimicrob Agents) - "Expression of the gene resulted in high-level of resistance to 4,5-disubstituted 2-deoxystreptamine (2-DOS) and to 4-monosubstituted 2-DOS aminoglycosides, as well as a moderate resistance to 4,6-disusbstituted 2-DOS aminoglycosides, including the last resort aminoglycoside plazomicin...The immediate genetic context of this methyltransferase suggests high relationship to the Eubacteriales order. This finding enlarges the list of the true pan-aminoglycoside 16S rRNA methyltransferases, that threaten the usefulness and development of next-generation aminoglycosides."

Journal

A Cell-Based Screening Assay for rRNA-Targeted Drug Discovery. (PubMed, ACS Infect Dis) - "Intermediate fluorescence was found with plazomicin, neamine, apramycin, ribostamicin, gentamicin, and amikacin. In contrast to planktonic cells, established biofilms yielded an average Z' factor of 0.61. The high sensitivity of this cell-based assay in a physiological context demonstrates significant potential for identifying potent new ribosomal binding antibiotics."

Journal • Infectious Disease

A dual-function chromogenic and fluorogenic benzofurazan probe for plazomicin and its innovative utility for development of two microwell assays with high throughput for analysis of drug substance and pharmaceutical formulations. (PubMed, RSC Adv) - "In conclusion, this study represents the first evaluation of NBD-F as a dual-function probe for the microwell-based photometric and fluorometric determination of PLZ. The developed assays serve as valuable analytical tools for the quality control of PLZ's bulk drug substance and pharmaceutical formulations."

Journal • Infectious Disease • Nephrology

Comparing the activity of broad-spectrum beta-lactams in combination with aminoglycosides against VIM-producing Enterobacteriaceae. (PubMed, Microbiol Spectr) - "In this study, we utilized the static time-kill assay to investigate clinically relevant concentrations of cefepime, piperacillin-tazobactam, and meropenem alone and in combination with either amikacin or the novel plazomicin to determine if combinations of routinely used beta-lactam therapy with an aminoglycoside would achieve bactericidal activity against eight clinically isolated Verona integron-encoded MBL (VIM)-producing CRE...Both aztreonam/avibactam and meropenem with either aminoglycoside were rapidly bactericidal within 4 hours and remained bactericidal through 24 hours against all isolates with few exceptions...Our results further our understanding of combination therapy options against VIM-producing CRE, including with non-carbapenem-beta-lactams cefepime and piperacillin. By optimizing combinations of existing antimicrobial agents, we hope to expand the available armamentarium against these resistant pathogens."

Combination therapy • Journal • Infectious Disease

Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates. (PubMed, Microorganisms) - "We examined the potency of 22 standard-of-care antibiotics and the newer antibiotics eravacycline, omadacycline, and plazomicin against these strains...We found that this collection is highly resistant to most or all standard-of-care antibiotics, except for minocycline and rifampin...We also identified two highly effective combinations, cefepime and amikacin and cefepime and ampicillin-sulbactam, which exhibited high rates of synergy against this collection. This information is valuable in our battle against highly drug resistant and virtually untreatable A. baumannii infections."

Journal • Infectious Disease

Efficacy of ceftazidime/avibactam and plazomicin on carbapenem-resistant Klebsiella pneumoniae and Escherichia coli. (PubMed, Acta Microbiol Immunol Hung) - "Susceptibility of imipenem, meropenem, ertapenem, ceftazidime/avibactam and plazomicin was investigated by broth-microdilution method. Ceftazidime/avibactam demonstrated a good efficacy among OXA-48 producing K. pneumoniae and E. coli, however, plazomicin had a significantly lower antibacterial effect in our study. Both antimicrobial agents should be considered as an option by evaluating combined susceptibility results and gene patterns obtained by regional and global molecular data in the treatment of CRE infections."

Journal • Infectious Disease • Pneumonia

Characterizing carbapenemase-producing Escherichia coli isolates from Spain: high genetic heterogeneity and wide geographical spread. (PubMed, Front Cell Infect Microbiol) - "Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections."

Heterogeneity • Journal • Infectious Disease

A Comprehensive Study on Species Specific Antimicrobial Resistance Gene Profiles in Clinical Isolates of Achromobacter Spp. Through Whole Genome Sequencing (ASM Microbe 2024) - "Phenotypic AST data showed high MIC for majority of antibiotics tested, lower MIC50 was seen for carbapenems, piperacillin/tazobactam and newer beta-lactamase combination agents. Of note, the MIC50 for the newer agents delafloxacin, plazomicin and omadacycline was suggested reduced activity, except eravacycline (70% isolates tested)...The multidrug efflux pump AxyXY-OprZ genes, were identified in all species except A. mucicolens. Our study concludes MALDI-TOF cannot accurately discriminate between a few species, and differences exist between the genotypic mechanisms of resistance in the various species within this genus."

Clinical • Whole genome sequencing • Infectious Disease

Intracellular Accumulation of Plazomicin in a Highly AGS-Resistant Klebsiella pneumoniae with 16S rRNA Methyltransferase ArmA (ASM Microbe 2024) - "To mechanistically enhance AMG-based combinations, we studied the impact of a BL/BLI (ceftazidime/avibactam, CAZ/AVI) on the accumulation kinetics of an AMG (plazomicin). Our ultra-sensitive UPLC-MS/MS assay allowed us to characterize the extensive (15.6 fold) intracellular accumulation of plazomicin in CR-Kp in the presence and absence of CAZ/AVI. We identified a bi-phasic accumulation kinetics. Future modeling analyses will explore more complex kinetics to evaluate potential self-promoted uptake and other mechanisms."

Infectious Disease • Pneumonia