The current strategy in treating multi-drug resistant gram-negative bacterial (MDR-GNB) infections is salvage therapy by using polymyxins. However, the beginning emergence of polymyxin resistance should enforce strict antimicrobial stewardship programs to preserve polymyxin efficacy. Knowledge of structural characteristics, pharmacodynamic, and pharmacokinetic profiles of polymyxins, as well as consideration of efficacy, safety, suitability, and cost, will help in the choice of the appropriate polymyxin for therapy. Polymyxin B is the recommended polymyxin for systemic use, while colistin is recommended for lower urinary tract infections, intraventricular, and intrathecal use. Either polymyxin can be used for hospital-acquired and ventilator-associated pneumonia. Combination therapy over monotherapy remains to be advantageous due to synergism and decreased resistance development. The choice of the second drug to be used should be based on full susceptibility, or if unavailable, a drug with the least minimum inhibitory concentration relative to the breakpoint set by the Clinical and Laboratory Standards Institute. Using the mnemonic ESCAPE can also guide physicians in their polymyxin prescription process: (1) Checking if the pathogen is Extensively resistant or multi-drug resistant; (2) checking the patient’s clinical status if compatible with Significant infection; (3) using Combination therapy; (4) ensuring Adequate dosing; (5) Proper preparation and administration of drug; and (6) keeping an Eye for response and adverse effects.
Polymyxin B ; Colistin ; Polymyxins

BACKGROUND: The emergence of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa has become a major problem. The use of nontraditional agents such as colistin and polymyxin B have been tried. The purpose of this study was to evaluate the colistin and polymyxin B susceptibility of A. baumannii and P. aeruginosa isolates in Korea. MATERIALS AND METHODS: According to susceptibility of ceftazidime and imipenem, selected 93 isolates of A. baumannii and 99 isolates of P. aeruginosa were collected from 5 university hospitals in Korea. Susceptibility to colistin and polymyxin B was tested using the reference broth microdilution method. RESULTS: The rates of other beta-lactams, aminoglycosides, and ciprofloxacin susceptibility were high (58-100%, 50-100%, and 75-100%, respectively) in ceftazidime- and imipenem-susceptible isolates but were low (< or =31%, < or =47%, and < or =18%, respectively) in ceftazidime- or imipenem-resistant isolates (P<0.05). Colistin and polymyxin B displayed a nearly identical spectrum of activity, exhibiting excellent potency against A. baumannii (MIC50/90, 1/2 microgram/mL) and P. aeruginosa (MIC50/90, 1/1 microgram/mL). Only one of the A. baumannii isolates was resistant to colistin (MIC, 4 microgram/mL), but the isolate was susceptible to polymyxin B (MIC, 2 microgram/mL). CONCLUSION: In Korea, no A. baumannii and P. aeruginosa isolates were resistant to both colistin and polymyxin B. These data suggested that polymyxins may be alternative drugs for multidrug-resistant A. baumannii and P. aeruginosa isolates.
Acinetobacter baumannii* ; Acinetobacter* ; Aminoglycosides ; beta-Lactams ; Ceftazidime ; Ciprofloxacin ; Colistin* ; Hospitals, University ; Imipenem ; Korea* ; Polymyxin B* ; Polymyxins* ; Pseudomonas aeruginosa* ; Pseudomonas*

BACKGROUND: The emergence of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa has become a major problem. The use of nontraditional agents such as colistin and polymyxin B have been tried. The purpose of this study was to evaluate the colistin and polymyxin B susceptibility of A. baumannii and P. aeruginosa isolates in Korea. MATERIALS AND METHODS: According to susceptibility of ceftazidime and imipenem, selected 93 isolates of A. baumannii and 99 isolates of P. aeruginosa were collected from 5 university hospitals in Korea. Susceptibility to colistin and polymyxin B was tested using the reference broth microdilution method. RESULTS: The rates of other beta-lactams, aminoglycosides, and ciprofloxacin susceptibility were high (58-100%, 50-100%, and 75-100%, respectively) in ceftazidime- and imipenem-susceptible isolates but were low (< or =31%, < or =47%, and < or =18%, respectively) in ceftazidime- or imipenem-resistant isolates (P<0.05). Colistin and polymyxin B displayed a nearly identical spectrum of activity, exhibiting excellent potency against A. baumannii (MIC50/90, 1/2 microgram/mL) and P. aeruginosa (MIC50/90, 1/1 microgram/mL). Only one of the A. baumannii isolates was resistant to colistin (MIC, 4 microgram/mL), but the isolate was susceptible to polymyxin B (MIC, 2 microgram/mL). CONCLUSION: In Korea, no A. baumannii and P. aeruginosa isolates were resistant to both colistin and polymyxin B. These data suggested that polymyxins may be alternative drugs for multidrug-resistant A. baumannii and P. aeruginosa isolates.
Acinetobacter baumannii* ; Acinetobacter* ; Aminoglycosides ; beta-Lactams ; Ceftazidime ; Ciprofloxacin ; Colistin* ; Hospitals, University ; Imipenem ; Korea* ; Polymyxin B* ; Polymyxins* ; Pseudomonas aeruginosa* ; Pseudomonas*

The effects and interactions of 4 beta-phorbol 12,13-dibutyrate(PDB) and polymyxin B(PMB) with adenosine on the electrically-evoked acetylcholine(ACh) release were studied in rat hippocampus. Slices from rat hippocampus were equilibrated with 3H-choline and the release of the labeled product, 3H-ACh, which was evoked by electrical stimulation(3Hz, 2ms, 5Vcm-1, rectangular pulses) was measured. PDB(0.3-10 micorM), a selective protein kinase C(PKC) activator, increased the evoked ACh release in a dose related fashion with an increase in the basal rate of release. The effects of 1(M PDB were significantly inhibited by 0.3 micorM tetrodotoxin(TTX) pretreatment or Ca++-free medium. PMB(0.03-1mg), a selective PKC inhibitor, decreased the ACh release in a dose dependent manner with an increase in the basal rate of release. Adenosine(1-10 micorM) decreased the ACh release without changing the basal rate or release, and this effect was significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine(2 micorM), a selective A1-receptor antagonist treatment. However, adenosine effects were not affected by PDB and PMB. These results indicate that the PKC play a role in the ACh release in the rat hippocampus but is not involved in the post-receptor mechanism of the A1-adenosine receptor.
Acetylcholine* ; Adenosine ; Animals ; Hippocampus* ; Polymyxin B ; Polymyxins ; Protein Kinase C* ; Protein Kinases* ; Rats* ; Tetrodotoxin

BACKGROUND: Infection caused by multi-drug resistant (MDR) Gram-negative organisms such as Pseudomonas and Acinetobacter species is one of emerging important problems in modern hospitals. To treat multi-drug resistant non-fermenting Gram-negatives, polymyxins which were used in 1960s, but abandoned because of grave toxicities such as renal toxicity are reused. The objective of this study was to estimate the probability of resistance development of the clinical isolates of Pseudomonas aeruginosa to polymyxins. METHODS AND MATERIALS: Twenty-nine multidrug-resistant P. aeruginosa isolates were collected from Dankook University Hospital and Seoul National University Hospital in 2000 and tested for antimicrobial susceptibility test, minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant frequency to ciprofloxacin and polymyxin B. RESULTS: The MIC50 and MIC90 of polymyxin B for the isolates were 2 and 2 microgram/mL, and those of ciprofloxacin were 0.5 and 4 microgram/mL, respectively. Thirteen of 29 isolates developed polymyxin B-resistant mutants but all 29 isolates, ciprofloxacin-resistant mutants. The MPC50 and MPC90 of polymyxin B were 32 and 64 microgram/mL, and those values of ciprofloxacin were 4 and 64 microgram/mL. Mutation frequencies of polymyxin B ranged from 2 x 10(-9) to 2 x 10(-7), and those of ciprofloxacin from 4 x 10(-10) to 5 x 10(-7). CONCLUSIONS: Mutation frequencies of polymyxin B were similar to those of ciprofloxacin, suggesting appreciable development of resistant mutants with wide usage of polymyxins.
Acinetobacter ; Ciprofloxacin ; Mutation Rate ; Polymyxin B* ; Polymyxins* ; Pseudomonas aeruginosa* ; Pseudomonas* ; Seoul

BACKGROUND: Infection caused by multi-drug resistant (MDR) Gram-negative organisms such as Pseudomonas and Acinetobacter species is one of emerging important problems in modern hospitals. To treat multi-drug resistant non-fermenting Gram-negatives, polymyxins which were used in 1960s, but abandoned because of grave toxicities such as renal toxicity are reused. The objective of this study was to estimate the probability of resistance development of the clinical isolates of Pseudomonas aeruginosa to polymyxins. METHODS AND MATERIALS: Twenty-nine multidrug-resistant P. aeruginosa isolates were collected from Dankook University Hospital and Seoul National University Hospital in 2000 and tested for antimicrobial susceptibility test, minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant frequency to ciprofloxacin and polymyxin B. RESULTS: The MIC50 and MIC90 of polymyxin B for the isolates were 2 and 2 microgram/mL, and those of ciprofloxacin were 0.5 and 4 microgram/mL, respectively. Thirteen of 29 isolates developed polymyxin B-resistant mutants but all 29 isolates, ciprofloxacin-resistant mutants. The MPC50 and MPC90 of polymyxin B were 32 and 64 microgram/mL, and those values of ciprofloxacin were 4 and 64 microgram/mL. Mutation frequencies of polymyxin B ranged from 2 x 10(-9) to 2 x 10(-7), and those of ciprofloxacin from 4 x 10(-10) to 5 x 10(-7). CONCLUSIONS: Mutation frequencies of polymyxin B were similar to those of ciprofloxacin, suggesting appreciable development of resistant mutants with wide usage of polymyxins.
Acinetobacter ; Ciprofloxacin ; Mutation Rate ; Polymyxin B* ; Polymyxins* ; Pseudomonas aeruginosa* ; Pseudomonas* ; Seoul

Severe sepsis and septic shock are the main causes of death in critically ill patients. Early detection and appropriate treatment according to guidelines are crucial for achieving favorable outcomes. Endotoxin is considered to be a main element in the pathogenic induction of gram-negative bacterial sepsis. Polymyxin B hemoperfusion can remove endotoxin and is reported to improve clinical outcomes in patients with intra-abdominal septic shock, but its clinical efficacy for pneumonic septic shock remains unclear. Here, we report a case of a 51-year-old man with pneumonic septic shock caused by Pseudomonas aeruginosa, who recovered through polymyxin B hemoperfusion.
Cause of Death ; Critical Illness ; Gram-Negative Bacteria* ; Hemoperfusion* ; Humans ; Middle Aged ; Polymyxin B* ; Polymyxins* ; Pseudomonas aeruginosa ; Sepsis ; Shock, Septic*

Severe sepsis and septic shock are the main causes of death in critically ill patients. Early detection and appropriate treatment according to guidelines are crucial for achieving favorable outcomes. Endotoxin is considered to be a main element in the pathogenic induction of gram-negative bacterial sepsis. Polymyxin B hemoperfusion can remove endotoxin and is reported to improve clinical outcomes in patients with intra-abdominal septic shock, but its clinical efficacy for pneumonic septic shock remains unclear. Here, we report a case of a 51-year-old man with pneumonic septic shock caused by Pseudomonas aeruginosa, who recovered through polymyxin B hemoperfusion.
Cause of Death ; Critical Illness ; Gram-Negative Bacteria ; Hemoperfusion ; Humans ; Middle Aged ; Polymyxin B ; Polymyxins ; Pseudomonas aeruginosa ; Sepsis ; Shock, Septic

Carbapenem-resistant Enterobacteriaceae (CRE) are now spread worldwide. In Korea, the number of CRE isolation is rapidly increasing, and impending endemicity is a concern. To cope well with CRE, thorough infection control, such as active surveillance, early detection, strict contact precaution, cleaning the environment, and antibiotic stewardship is very important. Therapeutic options include polymyxin, tigecycline, fosfomycin or the combination of them with carbapenem, which is currently the mainstay of treatment. In addition, various combination regimens with new carbapenemase inhibitors such as avibactam, vaborbactam, or relebactam, and other classes of antimicrobials such as plazomicin and siderophore cephalosporin are in the process of evaluation.
Carbapenems ; Enterobacteriaceae* ; Fosfomycin ; Infection Control ; Korea ; Polymyxins

Although shock in sepsis is usually managed successfully by conventional medical treatment, a subset of cases do not respond and may require salvage therapies such as veno-arterial extracorporeal membrane oxygenation (VA ECMO) support as well as an attempt to remove endotoxins. However, there are limited reports of attempts to remove endotoxins in patients with septic shock on VA ECMO support. We recently experienced a case of septic shock with severe myocardial injury whose hemodynamic improvement was unsatisfactory despite extracorporeal membrane oxygenation (ECMO) support. Since the cause of sepsis was acute pyelonephritis and blood cultures grew gram-negative bacilli, we additionally applied polymyxin B direct hemoperfusion (PMX-DHP) to the ECMO circuit and were able to successfully taper off vasopressors and wean off ECMO support. To the best of our knowledge, this is the first adult case in which PMX-DHP in addition to ECMO support was successfully utilized in a patient with septic shock. This case indicates that additional PMX-DHP therapy may be beneficial and technically feasible in patients with septic shock with severe myocardial injury refractory to ECMO support.
Adult ; Cardiomyopathies* ; Endotoxins ; Extracorporeal Membrane Oxygenation ; Hemodynamics ; Hemoperfusion* ; Humans ; Membranes* ; Oxygen* ; Polymyxin B* ; Polymyxins* ; Pyelonephritis ; Salvage Therapy ; Sepsis ; Shock ; Shock, Septic*