• Journal of Microbiology and Biotechnology
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• v.26 no.9
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• pp.1620-1628
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• 2016

In this study, we investigated colistin resistance mechanisms associated with the regulation of the pbgP operon in Klebsiella pneumoniae, using four isogenic pairs of colistin-susceptible strains and their colistin-resistant derivatives and two colistin-resistant clinical isolates. Amino acid sequence alterations of PhoPQ, PmrAB, and MgrB were investigated, and mRNA expression levels of phoQ, pmrB, pmrD, and pbgP were measured using quantitative real-time PCR. The phoQ and pmrB genes were deleted from two colistin-resistant derivatives, 134R and 063R. We found that phoQ, pmrD, and pbgP were significantly upregulated in all colistin-resistant derivatives. However, pmrB was significantly upregulated in only two colistin-resistant derivatives and one clinical strain. pmrB was not overexpressed in the other strains. The minimum inhibitory concentration of colistin was drastically lower in both phoQ- and pmrB-deleted mutants from a colistin-resistant derivative (134R) that was overexpressing phoQ and pmrB. However, colistin susceptibility was restored only in a phoQ-deleted mutant from a colistin-resistant derivative (063R) without overexpression of pmrB. In conclusion, two different regulations of the pbgP operon may associate with the development of colistinresisant K. pneumoniae.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.545-554
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• 2018

Background: The increasing morbidity and mortality rates associated with Acinetobacter baumannii are due to the emergence of drug resistance and the limited treatment options. We compared characteristics of colistin-resistant Acinetobacter baumannii (CR-AB) clinical isolates recovered from patients with and without prior colistin treatment. We assessed whether prior colistin treatment affects the resistance mechanism of CR-AB isolates, mortality rates, and clinical characteristics. Additionally, a proper method for identifying CR-AB was determined. Methods: We collected 36 non-duplicate CR-AB clinical isolates resistant to colistin. Antimicrobial susceptibility testing, Sanger sequencing analysis, molecular typing, lipid A structure analysis, and in vitro synergy testing were performed. Eleven colistin-susceptible AB isolates were used as controls. Results: Despite no differences in clinical characteristics between patients with and without prior colistin treatment, resistance-causing genetic mutations were more frequent in isolates from colistin-treated patients. Distinct mutations were overlooked via the Sanger sequencing method, perhaps because of a masking effect by the colistin-susceptible AB subpopulation of CR-AB isolates lacking genetic mutations. However, modified lipid A analysis revealed colistin resistance peaks, despite the population heterogeneity, and peak levels were significantly different between the groups. Conclusions: Although prior colistin use did not induce clinical or susceptibility differences, we demonstrated that identification of CR-AB by sequencing is insufficient. We propose that population heterogeneity has a masking effect, especially in colistin non-treated patients; therefore, accurate testing methods reflecting physiological alterations of the bacteria, such as phosphoethanolamine-modified lipid A identification by matrix-assisted laser desorption ionization-time of flight, should be employed.

• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.207-213
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• 2017

Background: It is recommended to use aerosolized (AS) colistin in patients undergoing mechanical ventilation therapy as an adjunctive in the latest guidelines, in spite of high nephrotoxicity and limited studies. In this study, systematic reviews and meta-analyzes were conducted to evaluate the safety and efficacy of AS colistin in patients with ventilator-associated pneumonia Methods: Two authors independently searched related literature published from Pubmed and EMBASE until July 2016 and included a study comparing adjunctive AS colistin with intravenous (IV) colistin monotherapy. The primary outcome was the clinical response rate, the secondary outcome was the overall mortality, and nephrotoxicity. The publication bias was evaluated using the Egger's test. Results: Of the total 279 articles, nine were finally included in the final analysis. There was a significant difference between the adjunctive AS colistin group and the IV colistin monotherapy group for the treatment-response rate (odds ratio (OR), 1.56; 95% CI, 1.14-2.14; p = 0.005; $I^2=36%$), although there was no significant difference in overall mortality (OR, 0.77; 95% CI, 0.57-1.04; p = 0.09; $I^2=20%$). However, there was no significant difference between the two groups in nephrotoxicity (OR, 1.13; 95% CI, 0.74-1.74; p = 0.57; $I^2=4%$). Conclusion: The addition of aerosolized colistin to IV colistin monotherapy showed better results in terms of efficacy than IV colistin monotherapy and did not show any significant difference in terms of total mortality and nephrotoxicity. Additional large-scale studies of this need to be verified.

• Journal of Veterinary Clinics
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• v.14 no.2
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• pp.215-222
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• 1997

Enrofloxacin-colistin combination, widely used in Gram negative infections in veterinary sector, was investigated in terms of MIC and initial killing rate using E coli k 88ab, Salmonella typhimurium, Pasteurella multocida type A, Bordetella bronchiseptica and Staphylococcus aureus as test organisms. On the basis of MICs of enrofloxacin-colistin combination against the above bacteria, killing rates of the combination of enrofloxacin and colistin at the ratio of 5:0, 4:1, 3:2, 1:1, 2:3, 1:4 and 0:5, indicated high and rapid antibacterial acitivities against all but Staphylococcus aureus R-209, with the number of bacteria reducing to less than one percent within two hours. At the MIC of enrofloxacin or colistin, both antibacterials showed the highest killing rates during 2-4 hours against Gram negatives such as E coli K88ab,Pasteurella multocida type A and Bodetella bronchiseptica but allowed the regrowth of the same pathogens thereafter. On the while, the combination of two antibacterials at a fourth MIC resulted in high killing rate without bacterial regrowth during 24 hours, suggesting the synergistic antivacterial effects. The combination, however, did not show favourable activity against Gram negatime S typhimurium and Gram positive S aureus ergistic antibacterial activity against Gram negatime pathogens but also colistin showed LPS-neutraization, we could suggest the combination should provide clinically positive therapeutic armarium in Gram negative infections.

• Pediatric Infection and Vaccine
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• v.27 no.1
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• pp.45-52
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• 2020

Purpose: This pilot study aimed to evaluate the efficacy of high dose ampicillin-sulbactam and colistin combination therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in the pediatric intensive care unit of Pusan National University Children's Hospital. Methods: We retrospectively reviewed 17 pediatric patients with VAP caused by CRAB from June 2017 to August 2018. Ten (58.8%) patients were treated with high dose ampicillin-sulbactam and colistin combination therapy (combination therapy group), whereas 7 were treated with colistin only or with various combinations with or without colistin (other antibiotics group). Clinical and bacteriological outcomes were compared between the groups. Results: The mean duration of fever after antibiotic use was 1.30±1.70 days in the combination therapy group and 1.71±1.49 days in the other antibiotics group. The mean duration of days for negative conversion of endotracheal aspirate bacterial culture after antibiotic therapy was 3.40±1.71 days in the combination therapy group and 11.80±8.86 days in the other antibiotics group. The mortality rate within 30 days of antibiotic therapy was 1/10 (10%) in the combination therapy group and 3/7 (42.9%) in the other antibiotics group. Conclusions: High dose ampicillin-sulbactam and colistin combination therapy as early antibiotic treatment in VAP caused by CRAB in children could improve clinical outcomes.

• 한국생물공학회:학술대회논문집
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• 2002.04a
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• pp.224-227
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• 2002

Colistin produced from Penibacillius polymyxa was widely used as an antibiotic active against gram-negative bacteria and as feed additive. This research studied on increment of colistin productivity by mutation of P. polymyxa. As a result, several mutants were obtained from the strain by UV radiation and NTG treatment. They produced approximately 8.5${\sim}$9.0 g/L of colistin in flask and jar culture. Colistin productivity of the mutant, named Penibacillius polymyxa CBY, showed 100 times than that of wild type. When Penibacillius polymyxa CBY fermented in the optimal medium, it produced up to 18 g/L of colistin in jar fermentation.

• Tuberculosis and Respiratory Diseases
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• v.64 no.1
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• pp.8-14
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• 2008

Background: Acinetobacter infections are difficult to treat as they often exhibit multiple resistance to the antibiotics that are currently available for the treatment of pneumonia. Colistin is active against gram-negative bacteria, including the multiple drug resistant (MDR) Acinetobacter species. However, intravenous administration of colistin was abandoned because of its nephrotoxicity and neurotoxicity. The aims of this study were to examine the efficacy and safety of colistin administered by aerosol in the treatment of pneumonia caused by MDR Acinetobacter baumannii. Methods: We retrospectively reviewed the medical records of patients admitted to the intensive care unit (ICU) from Dec. 2006 to Aug. 2007 who had been diagnosed as suffering from pneumonia due to MDR Acinetobacter baumannii and had been treated with nebulized colistin. Results: 31 patients received aerosolized colistin. The average duration of the treatment was $14{\pm}7$ days and the daily dose of ranged from 225 mg to 300 mg. All patients received concomitant intravenous antimicrobial agents. The average length of the stay in the ICU was $34{\pm}21$ days and in the hospital $58{\pm}52$ days. The overall microbiological eradication was observed in 25 patients (80.6%). 14 of these (56%) were cured, and 11 (44%) were infected with other microorganisms. The overall crude mortality of the ICU was 48%. Nephrotoxicity and significant bronchial constriction did not occur in any patient during neublized colistin treatment. Conclusion: Nebulized colistin may be a safe and effective option in the treatment of pneumonia due to MDR Acinetobacter baumannii. Its role in therapy warrants further investigation in comparative studies.

• Journal of Microbiology
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• v.45 no.4
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• pp.358-363
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• 2007

Multi-drug resistant Pseudomonas aeruginosa has been implicated in a variety of serious therapeutic problems in clinical environments. Among the 968 P. aeruginosa isolates obtained from two hospitals in Daegu, Korea, we acquired 17 isolates that were resistant to all available tested antimicrobial agents, with the exception of colistin (colistin-only sensitive). We characterized the antimicrobial susceptibilities, $metallo-{\beta}-lactamases$, and epidemiological relatedness among the colistin-only sensitive P. aeruginosa isolates. All colistin-only sensitive isolates were positive in the modified Hodge test and imipenem-EDTA synergy test, thereby indicating the production of $metallo-{\beta}-lactamases$. 11 isolates from the secondary hospital and six isolates from the tertiary teaching hospital harbored $bla_{VIM-2}$ and $bla_{IMP-1}$, respectively. The pulsed-field gel electrophoretic analysis of the SpeI-digested DNA from P. aeruginosa isolates indicated that two different clones of colistin-only sensitive P. aeruginosa originated from each hospital, and had spread within the hospital environment. Overall, colistin-only sensitive P. aeruginosa was detected in Korea for the first time, but no pan-drug resistant bacteria were identified. Nationwide surveillance is required in order to monitor the emergence of colistin-only sensitive or pan-drug resistant bacteria.

• Korean Journal of Veterinary Research
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• v.15 no.1
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• pp.101-108
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• 1975

The susceptibility of 536 isolates of Staphylococcus and 313 isolates of Streptococcus to a number of chemotherapeutics were studied. These organisms were isolated from bovine mastitis during 1973 and 1974. In addition to this, the rate of multiple resistance of 425 isolates of Staphylococcus and 164 isolates of Streptococcus, isolated in 1974, to the chemotherapeutics was analysed. The results obtained in this work were summerized as follows: 1. Staphylococcus and Streptococcus isolated in 1974 showed a higher resistance, with 3 exceptions of chemotherapeutics, than the isolates of 1973. 2. Staphylococcus isolated in 1973 and 1974 showed a higher susceptibility than Streptococcus. 3. The strains of Staphylococcus resistant to colistin were 39 strains (9.2%), to colistin and sulfisoxazole 33 (7.8%), to streptomycin, kanamycin, colistin and sulfisoxazole 20 (4.7%), and to penicillin, colistin and sulfisoxazole 18 (4.2%). 4. The strains of Streptococcus resistant to colistin were 17 strains (10.4%), to streptomycin, kanamycin, colistin and sulfisoxazole 13 (7.9%), to colistin and sulfisoxazole 11 (6.7%) and to penicillin, colistin and sulfisoxazole 11 (6.7%).

• Toxicological Research
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• v.13 no.1_2
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• pp.111-116
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• 1997

In the present study, we investigated the neutralization activity of various antimicrobials against lipopolysaccharide (LPS) as well as interaction between two antimicrobials (enrofioxacin and coilstin) using checkerboard method. The neutralization activity of antimicrobials used in the test was assayed by means of LAL chromogenic test after reaction of LPS with colistin, enorfioxacin, ampicillin, polymyxin B, oxytetracycline, streptomycin, and erythromycin. As the results, the neutralization activity of coltstin and polymixin B had a more stronger than that of tested other antimicrobials. In bacterial culture broth, the best neutralization activity of the antibiotics was also shown to coltstin and polymixin B. Meanwhile, It was shown to have synergism between enorfloxacin and coltstin on the basts of FIC (fractional inhibition concentration). The FIC of enorfioxacin-colistin combinations was 0.50-1.03 to Staphylococcus aureus R-209, 1.03-1.06 to Salmonella typhimurium, 0.75-1.25 to Bordetella Bronchtseptica and 1.02-1.25 to E. coli K88ab. On the basts of the above results, the present study may be of clinical usefulness in the choice of an antibiotic therapy for severe sepsts in animals.