China
Africa
Explore chapters and articles related to this topic
Plazomicin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Plazomicin has in vitro antibacterial activity against many antibiotic-susceptible and antibiotic-resistant Gram-negative pathogens. Clinically important enteric bacteria such as Citrobacter spp., Escherichia coli, Klebsiella spp., Enterobacter spp., and Serratia spp. are generally inhibited with MIC90 values in the range of 0.5–2 mg/l (Aggen et al., 2010; Almaghrabi et al., 2014; Endimiani et al., 2009; Galani et al., 2012; Landman et al., 2010; Landman et al., 2011; Livermore et al., 2011; Rodriguez-Avial et al., 2015; Walkty et al., 2014). Proteus spp. and Morganella spp. are less sensitive to plazomicin, with MIC90 values of 4 to 8 mg/l and 8–64 mg/l, respectively (Aggen et al., 2010; Kotlovsky et al., 2011; Castanheira et al., 2015). The range of plazomicin MICs against Salmonella and Shigella spp. is 0.5–8 mg/l, with an MIC90 of 8 mg/l, similar to the Proteae (Aggen et al., 2010). Activity against nonfermentative bacteria is generally less than against Enterobacteriaceae. Plazomicin MIC50 values can range from 2–16 mg/l against Pseudomonas aeruginosa and Acinetobacter spp., with plazomicin MIC90 values of 16–32 mg/l for recent collections of P. aeruginosa and 16 mg/l for Acinetobacter spp. from the USA and Europe (Aggen et al., 2010; Landman et al., 2011; Walkty et al., 2014; Castanheira et al., 2015; Garcia-Salguero et al., 2015). The compound is inactive against Stenotrophomonas maltophilia with MIC50/MIC90 values of 64/>64 mg/l (Walkty et al., 2014).
Pharmacotherapeutic advances for recurrent urinary tract infections in women
Published in Expert Opinion on Pharmacotherapy, 2020
Mohamad Moussa, Mohamed Abou Chakra, Athanasios Dellis, Yasmin Moussa, Athanasios Papatsoris
Plazomicin is a novel semi-synthetic parenteral aminoglycoside that inhibits bacterial protein synthesis. It has been approved by the FDA for use in adults with cUTIs, including pyelonephritis. Plazomicin displays potent in vitro activity against Enterobacteriaceae, including both ESBL- and CRE-isolates. It has superior activity compared with traditional aminoglycosides and potentially improved efficacy and decreased toxicity compared with colistin [141]. The most common adverse reactions include decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, and hypotension. As with other aminoglycosides, plazomicin may cause neuromuscular blockade, ototoxicity, and fetal harm in pregnant women. Due to limited efficacy and safety data, plazomicin is indicated for the treatment of cUTIs in adults with limited or no alternative treatment options, using a dosage regimen of 15 mg/kg intravenously every 24 hours for 4–7 days [142]. A phase 3 trial (EPIC trial) was conducted. Patients with cUTIs were assigned, in a 1:1 ratio to receive intravenous plazomicin (15 mg per kilogram of body weight once daily) or meropenem (1 g every 8 hours), with optional oral step-down therapy after at least 4 days of intravenous therapy, for a total of 7–10 days. Plazomicin was non-inferior to meropenem with respect to the primary efficacy end points. On day 5, a composite cure was observed in 88.0% of the patients in the plazomicin group and in 91.4% in the meropenem group [143].
Developments on antibiotics for multidrug resistant bacterial Gram-negative infections
Published in Expert Review of Anti-infective Therapy, 2019
Georgios L. Voulgaris, Maria L. Voulgari, Matthew E. Falagas
Plazomicin is a new semisynthetic member of aminoglycoside family and is produced by the derivatization of sisomicin [93]. Like the other aminoglycosides, plazomicin owes its bactericidal activity to the ability to inhibit the bacterial protein synthesis by binding to the 30 s ribosomal subunit [94]. The novel structural modifications incorporated in plazomicin preserve molecular stability in the presence of diverse aminoglycoside-modifying enzymes (AMEs) that provide resistance to common aminoglycosides [95]. Plazomicin also exhibited a prolonged post-antibiotic effect against MDR Enterobacteriaceae, maintaining suppression of bacterial growth ranging from 0.2 to >4.5 h after the plazomicin levels fell below MIC [96]. However, the bacterial expression of ribosomal methyltransferases confers resistance to plazomicin [97].
The antibiotic arms race: current and emerging therapy for Klebsiella pneumoniae carbapenemase (KPC) - producing bacteria
Published in Expert Opinion on Pharmacotherapy, 2018
Michael E. Plazak, Pranita D. Tamma, Emily L. Heil
The CARE trial randomized 39 patients with documented or presumed CRE infection to receive plazomicin 15 mg/kg every 24 h or colisitin 300 mg loading dose followed by a 5 mg/kg/day maintenance regimen. Both groups received either concomitant meropenem or tigecycline. All-cause mortality was 12% in the plazomicin-treated patients compared to 40% in the colistin-treated patients. Plazomicin was associated with a more favorable response at the completion of therapy (93% vs. 60%) as well as 7 days later (93% vs. 53%). Additionally, more patients in the colistin-treated group had serum creatinine elevations ≥0.5 mg/dL compared to patients in the plazomicin group [88]. Although complete study results are pending, the low mortality rate, high-level of efficacy, and minimal toxicity displayed in this preliminary analysis are promising. Given its in vitro activity against KPC-producers and the preliminary results from CARE, plazomicin could soon find a place among a highly active combination regimen against BSIs caused by KPC-producing Enterobacteriaceae. Additionally, plazomicin may find a role as a monotherapy option for KPC-producing UTIs, given its ability to highly concentrate in the urine.