An estimated 9,437 and 7,941 CRE infections were treated with an intravenous
polymyxin or new agent, respectively, from February 2018 to January 2019, representing about 28 and 23 percent of CRE infections, respectively.
The antibiotics used were
polymyxin B (PB 300mg), doxycycline (DO 30mg), gentamicin (CN 10mg), amikacin (AK 30mg), imipenem (IMP 10mg), ciprofloxacin (CIP 5mg), meropenem (MEM 10mg), trime thoprim/sulmethoxazole (SXT 25mg), sulzone (SCF), minocycline (MH 30mg), chloramphenicol (C 30mg), vancomycin (VA 30mg), linezolid (LZD 30mg), erythromycin (E 15mg), ceftazidime (CAZ 30mg), and aztreonam (ATM 30mg).
However, clinicians have reevaluated and endorsed older therapeutic agents such as
polymyxin B, a bactericidal antibiotic derived from Bacillus polymyxa to treat infections by MDR GNB, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii (25-28).
Rather than monotherapy, clinicians are increasingly resorting to combination therapies, such as dual carbapenems, carbapenems combined with
polymyxin B or tigecycline.
In Citrobacter spp resistance to
polymyxin, aminoglycoside, quinolones, linezolid, vancomycin, macrolides, licosamide was 100% while 50% isolates were resistant to penicillin.
M2 EQUITYBITES-March 6, 2018-MicuRx awarded CARB-X's grant for innovative
polymyxin antibiotic MRX-8
M2 PHARMA-March 6, 2018-MicuRx awarded CARB-X's grant for innovative
polymyxin antibiotic MRX-8
Until recently, all mechanisms described were of chromosomal origin, mostly mediated by the two-component systems PmrAB and PhoPQ, leading to the addition of positively charged carbohydrates on the negatively charged lipid A (Figure 1), a phosphoethanolamine by a phosphoethanolamine transferase or a 4-amino-4-arabinose by surexpression of arnBCADTEF operon, leading to the loss of
polymyxin affinity for the LPS [5].
The following antibiotic discs were tested: ceftazidime (30 [micro]g), cefepime (30 [micro]g), piperacillin-tazobactam (100 [micro]g/10 [micro]g), Imipenem (10 [micro]g), Meropenem (10 [micro]g), Gentamicin (10 [micro]g), Amikacin (30 [micro]g), Ampicillin-sulbactam (10 [micro]g/10 [micro]g), Cotrimoxazole (25 [micro]g), aztreonam (30 [micro]g), Ciprofloxacin (5 [micro]g), Norfloxacin (30 [micro]g) (for urinary isolates),
Polymyxin B (300 units), and Colistin (10 [micro]g).
The following antibiotics were included: amoxicillin, amoxicillin-clavulanic acid (AMC), piperacillin, piperacillin-tazobactam (TZP), mezlocillin, mezlocillin-sulbactam (MSU), cefazolin, cefuroxime, ceftriaxone, cefotaxime, ceftazidime, cefoperazone, cefoperazone-sulbactam (CSL), cefepime, aztreonam, moxalactam, imipenem, meropenem, panipenem, ertapenem, gentamycin, amikacin, tetracycline, minocycline, tigecycline, ciprofloxacin, levofloxacin, nitrofurantoin, fosfomycin,
polymyxin B, and colistin.
(1) Of these alternative classes,
polymyxin and tigecycline (TGC) remain the most active treatments in vitro against MDR A.
Polymyxins which include
polymyxin B and colistin (
polymyxin E) are the "old" antibiotics which are used clinically.