plazomicin
Regulatory sources consulted
Approved indications
- Complicated urinary tract infections, including pyelonephritis, caused by susceptible gram-negative organisms in adults with limited options.
Contraindications
Absolute
- Hypersensitivity to plazomicina or other aminoglycosides.
Clinical warnings
- It may cause nephrotoxicity, irreversible cochlear or vestibular ototoxicity, and neuromuscular blockade; monitor renal function, hearing, balance, and serum concentrations. — DailyMed, set_id eccf9fd9-53ac-4252-a106-5567b3a82a70
- Major warning · Risk increases with high doses, prolonged treatment, dehydration, older age, renal impairment, and other nephrotoxic or ototoxic drugs. — DailyMed, set_id eccf9fd9-53ac-4252-a106-5567b3a82a70
Drug interactions
- HighOther nephrotoxic or ototoxic drugs
Mechanism: Renal, cochlear, and vestibular toxicity may be additive.
Recommendation: Avoid the combination if possible; if essential, intensify TDM, creatinine monitoring, and audiometry.
DailyMed, set_id eccf9fd9-53ac-4252-a106-5567b3a82a70
- HighLoop diuretics
Mechanism: They may increase ototoxicity, especially with rapid intravenous administration.
Recommendation: Avoid the combination or closely monitor hearing and renal function.
DailyMed, set_id eccf9fd9-53ac-4252-a106-5567b3a82a70
- HighNeuromuscular blockers and anesthetics
Mechanism: Neuromuscular blockade may be potentiated and cause apnea.
Recommendation: Monitor respiratory function and have ventilatory support and calcium or neostigmine available.
DailyMed, set_id eccf9fd9-53ac-4252-a106-5567b3a82a70
Adverse events
Common (≥1%)
Decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, and hypotension
Rare but serious
Renal failure, irreversible hearing loss, vestibular toxicity, and neuromuscular blockade with apnea
Pregnancy and lactation
It may cause fetal harm; advise about risk and avoid during pregnancy unless benefit clearly outweighs risk. Milk data are insufficient; consider discontinuing breastfeeding or treatment.
Recent literature (PubMed)
Pneumonia is frequently encountered in clinical practice, and Gram-negative bacilli constitute a significant proportion of its aetiology, especially when it is acquired in a hospital setting. With the alarming global rise in multidrug resistance in Gram-negative bacilli, antibiotic therapy for treating patients with pneumonia is challenging and must be guided by in vitro susceptibility results. In this review, we provide an overview of antibiotics newly approved for the treatment of pneumonia caused by Gram-negative bacilli. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam have potent activity against some of the carbapenem-resistant Enterobacterales, especially Klebsiella pneumoniae carbapenemase producers. Several novel antibiotics have potent activity against multidrug-resistant Pseudomonas aeruginosa, such as ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relabactam and cefiderocol. Cefiderocol may also play an important role in the management of pneumonia caused by Acinetobacter baumannii, along with plazomicin and eravacycline. Plazomicin is an aminoglycoside antibiotic similar to gentamicin and amikacin. No information is available on the use of plazomicin during breastfeeding. However, based on the excretion of other aminoglycoside antibiotics, amounts in milk are expected to be low. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (e.g., thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.
Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for a variety of community and hospital infections. Infections caused by carbapenem-resistant K. pneumoniae (CRKP) constitute a major threat for public health and are strongly associated with high rates of mortality, especially in immunocompromised and critically ill patients. Adhesive fimbriae, capsule, lipopolysaccharide (LPS), and siderophores or iron carriers constitute the main virulence factors which contribute to the pathogenicity of K. pneumoniae. Colistin and tigecycline constitute some of the last resorts for the treatment of CRKP infections. Carbapenemase production, especially K. pneumoniae carbapenemase (KPC) and metallo-β-lactamase (MBL), constitutes the basic molecular mechanism of CRKP emergence. Knowledge of the mechanism of CRKP appearance is crucial, as it can determine the selection of the most suitable antimicrobial agent among those most recently launched. Plazomicin, eravacycline, cefiderocol, temocillin, ceftolozane-tazobactam, imipenem-cilastatin/relebactam, meropenem-vaborbactam, ceftazidime-avibactam and aztreonam-avibactam constitute potent alternatives for treating CRKP infections. The aim of the current review is to highlight the virulence factors and molecular pathogenesis of CRKP and provide recent updates on the molecular epidemiology and antimicrobial treatment options.
Carbapenem resistant Enterobacterales (CRE) are a major threat to global health and hospital-onset CRE infections have risen during the COVID-19 pandemic. Novel antimicrobials are now available for the treatment of CRE infections. There remains an urgent need for new antimicrobials for CRE, especially for those producing metallo-β-lactamases. This article discusses previously published research supporting currently available novel antimicrobials for the treatment of CRE infections. Newer compounds currently being evaluated in clinical trials are covered. A literature search was conducted in PubMed over all available dates for relevant published papers and conference abstracts with the search terms, 'CRE,' 'carbapenem-resistant Enterobacterales,' 'β-lactam-β-lactamase inhibitor,' 'KPC,' 'NDM,' 'metallo-β-lactamase,' 'ceftazidime-avibactam,' 'meropenem-vaborbactam,' 'imipenem-cilastatin-relebactam,' 'cefiderocol,' 'eravacycline,' 'plazomicin,' 'taniborbactam,' 'zidebactam,' and 'nacubactam.' Novel antimicrobials for CRE infections have been developed, most notably the β-lactam-β-lactamase inhibitor combinations, though treatment options for infections with metallo-β-lactamase producing Enterobacterales remain few and have limitations. Development of antibiotics with activity against metallo-β-lactamase producing Enterobacterales is eagerly awaited, and there are promising new compounds in clinical trials. Finally, more clinical research is needed to optimize and individualize treatment approaches, which will help guide antimicrobial stewardship initiatives aimed at reducing the spread of CRE and development of further resistance.
Aim: Compared with uncomplicated urinary tract infections (UTIs), complicated UTIs (cUTIs) including acute pyelonephritis (AP) present with significant morbidity, a higher risk of treatment failure and typically require longer courses of treatment, or alternative antibiotics. The emergence of drug-resistant organisms represents a considerable challenge in the treatment of patients with cUTIs/AP and has limited antibiotic options. Carbapenems are considered the current last line of therapy, however, carbapenem resistance represents a growing problem. Although several established and novel treatment options are available, direct comparative evidence is lacking. Methods: Randomized controlled trials (RCTs) were identified by systematic literature review of Embase®, MEDLINE® and Cochrane databases (database inception to 15th June 2022). Relevant conference proceedings (2020-2022) were also reviewed. Following feasibility assessment to verify network connectivity at an overall level, outcome specific networks were prepared. Bayesian network meta-analysis (NMA) was performed (using R version 4.2.1) to determine the relative efficacy of various treatments for cUTI/AP, including cefepime + enmetazobactam. Convergence was assessed by visual inspection of trace plots. The accuracy of the posterior estimates was assessed using the Monte Carlo error for each parameter. Published study results were included in the synthesis of the relative risk (RR) of efficacy end points, using a logit link with binomial likelihood distribution. Results: Feasibility assessment was conducted for 40 RCTs identified, to assess the viability of constructing a network of interlinked RCTs. Of those, 28 studies were included in the master NMA network. A fixed effects model (FEM) was selected due to low statistical heterogeneity, according to I2 values. For composite outcome at test of cure (TOC), ceftolozane + tazobactam, cefepime + enmetazobactam, cefiderocol, levofloxacin and plazomicin demonstrated