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 ability of Bacillus subtilis, strain ALICA to produce three mycolytic enzymes (chitinase, β-1,3-glucanase, and protease), was carried out by the chemical standard methods. Bacillus subtilis ALICA was screened based on their antifungal activity in dual plate assay and cell-free culture filtrate (25%) against five different phytopathogenic fungi Alternaria alternata, Macrophomina sp., Colletotrichum gloeosporioides, Botrytis cinerea, and Sclerotium rolfesii. The B. subtilis ALICA detected positive for chitinase, β-1,3-glucanase and protease enzymes. Fungal growth inhibition by both strain ALICA and its cell-free culture filtrate ranged from 51.36% to 86.3% and 38.43% to 68.6%, respectively. Moreover, hyphal morphological changes like damage, broken, swelling, distortions abnormal morphology were observed. Genes expression of protease, β-1,3-glucanase, and lipopeptides (subtilosin and subtilisin) were confirmed their presence in the supernatant of strain ALICA. Our findings indicated that strain ALICA provided a broad spectrum of antifungal activities against various phytopathogenic fungi and may be a potential effective alternative to chemical fungicides.
Alternaria ; Bacillus subtilis* ; Bacillus* ; Botrytis ; Chitinase ; Colletotrichum ; Fungi* ; Lipopeptides ; Prosopis*

Cyclic lipopeptide, also named as acylpeptide, which was characteristic with novel structures, was paid more attention in the recent years. Cyclic lipopeptide showed various bioactivities including antibacterial, anti-tumor, anti-inflammatory, etc. Cyclic lipopeptide originated mainly from the second metabolites of microorganism, such as Cyanobacterium, Bacterium, Actinomyces, etc. The bacteria included the genus of Bacillus and Pseudomonas. In this account, the review has been made on the development of cyclic lipopeptide.
Anti-Bacterial Agents ; pharmacology ; Antibiotics, Antineoplastic ; pharmacology ; Bacillus ; chemistry ; Cyanobacteria ; chemistry ; Daptomycin ; isolation & purification ; pharmacology ; Humans ; Lipopeptides ; chemistry ; isolation & purification ; pharmacology ; Peptides, Cyclic ; chemistry ; isolation & purification ; pharmacology ; Pseudomonas ; chemistry

Echinocandins ; therapeutic use ; Humans ; Infant, Newborn ; Infant, Premature ; Lipopeptides ; Mycoses ; drug therapy ; Sepsis ; drug therapy ; microbiology

Antifungal Agents ; therapeutic use ; Echinocandins ; therapeutic use ; Humans ; Infant, Newborn ; Infant, Premature ; Lipopeptides ; Mycoses ; drug therapy

Bacillus spp. are probiotics and can secrete a variety of natural antimicrobiol active substances, of which lipopeptides are an important class. Up to now, about 90 lipopeptides have been identified, and most of them are cyclic lipopeptides. surfactin, iturin, fengycin, bacillomycin and polymyxins are widely studied, and the first three have huge potential for application due to their properties of surfactants and anti-fungal, anti-bacterial, anti-viral, anti-tumor and anti-inflammatory functions. In this paper, the research progress in the structure, function, synthesis regulation, separation, purification and production of surfactin, iturin and fengycin was reviewed. Synthetic biology is a vital means to increase the yield of lipopeptides, and in the future, lipopeptides can be used in crop cultivation, animal farming, food, medicine and petroleum industries as well as environmental protection. Future research should be strengthened on the discovery of new lipopeptides, synthesis of high-activity lipopeptides, economical production of lipopeptides on a large scale and their safety evaluation.
Anti-Bacterial Agents ; Anti-Infective Agents/pharmacology* ; Bacillus ; Bacillus subtilis ; Lipopeptides/pharmacology* ; Peptides, Cyclic/pharmacology*

Surfactin has great potential applications in enhancing oil recovery, agriculture, pharmaceuticals, foods and beverages, and cosmetics due to its extraordinary surface activity, biodegradability, anti-bacterial activity and biocompatibility. Enhancing surfactin production by engineering surfactin-producer and optimizing culture conditions is the key of its industrial production and subsequent applications. In this study, the effect of fatty acid synthesis pathway on surfactin synthesis was investigated, and Bacillus subtilis THBS-2 and THBS-8 with high surfactin titer were constructed by overexpressing key genes involved in the fatty acid synthesis pathway. To optimize culture condition, the amount and adding time of isopropyl-beta-D-thiogalactopyranoside (IPTG) and amino acids were studied, and a two-stage culture method was obtained: IPTG (final concentration: 1.25 mmol/L) and leucine (final concentration: 5 g/L) were added at 3 h, leucine (final concentration 5 g/L) and condensed culture medium (5 mL) were added at 24 h. Applying this strategy, the surfactin titer of B. subtilis THBS-2 reached to 24 g/L in shake flask at 48 h and up to 34 g/L after 68 h fermentation in a 30-L fermentor. The results provide basis for large-scale production and broad application of surfactin.
Amino Acids ; Bacillus subtilis/metabolism* ; Culture Media ; Fermentation ; Lipopeptides ; Peptides, Cyclic

A Bacillus sp. BS061 significantly reduced disease incidence of gray mold and powdery mildew. To identify the active principle, the culture filtrate was partitioned between butanol and water. The antifungal activity against B. cinerea was evident in the butanol-soluble portion, and active substances were identified as cyclic lipopeptides, iturin A series, by nuclear magnetic resonance spectrometry (NMR) and mass analysis. Interestingly, antifungal activity against powdery mildew was observed in the water-soluble portion, suggesting that cyclic lipopeptides have no responsibility to suppress powdery mildew. This finding reveals that biocontrol agents of Bacillus origin suppress gray mold and powdery mildew through the secretion of different bioactive substances.
Bacillus* ; Fungi* ; Incidence ; Lipopeptides ; Magnetic Resonance Spectroscopy ; Peptides, Cyclic ; Spectrum Analysis ; Water