In vitro activity of ceftazidime-avibactam combined with colistin against extensively drug-resistant Pseudomonas aeruginosa.
10.3760/cma.j.issn.2095-4352.2019.10.007
- Author:
Qing MEI
1
;
Shike GENG
;
Xiaowei FANG
;
Yuxi HE
;
Lu LIU
;
Mingyan XU
;
Chunyan ZHU
;
Aijun PAN
Author Information
1. Department of Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China, Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, Anhui, China. Corresponding author: Pan Aijun, Email: aijunpan868@sina.com.
- Publication Type:Journal Article
- MeSH:
Anti-Bacterial Agents/therapeutic use*;
Azabicyclo Compounds/therapeutic use*;
Ceftazidime/therapeutic use*;
Colistin/therapeutic use*;
Drug Combinations;
Drug Resistance, Bacterial/genetics*;
Microbial Sensitivity Tests;
Pseudomonas Infections/drug therapy*;
Pseudomonas aeruginosa;
beta-Lactamases
- From:
Chinese Critical Care Medicine
2019;31(10):1212-1218
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To evaluate the in vitro activity of ceftazidime-avibactam (CAZ-AVI) alone or in combination with colistin (COL) against clinically isolated extensively drug-resistant Pseudomonas aeruginosa (XDR-PA).
METHODS:Minimum inhibitory concentration (MIC) of 16 clinical XDR-PA isolates was determined by broth dilution method and chessboard design when CAZ-AVI and COL were used alone or in combination, then the combined inhibitory concentration index (FICI) was calculated. Class A [Klebsiella pneumoniae carbapenemase β-lactamase (blaKPC), Guiana extended-spectrum β-lactamase (blaGES)], Class B [imipenemase β-lactamase (blaIMP), Verona-Integronmetallo β-lactamase (blaVIM), New Delhi metallo β-lactamase (blaNDM), German imipenemase β-lactamase (blaGIM), Sao Paulo metallo-β-lactamase (blaSPM)], Class C [AmpC β-lactamase (blaAmpC)], Class D [oxacillinase β-lactamase (blaOXA)] β-lactamase-related resistance genes were detected by polymerase chain reaction. Drug-resistant mutation frequencies of each strain were determined on a drug-containing plate. The time kill curves of three XDR-PA were plotted by colony counting method. A biofilm model was established in vitro, and the synergistic effect of CAZ-AVI and COL on biofilm inhibition was detected by methythiazolyl tetrazolium assay (MTT).
RESULTS:The MICs of 16 XDR-PA for CAZ-AVI ranged from 1 mg/L to 128 mg/L, and three of the isolates showed resistance (MIC > 8 mg/L). The FICI range of CAZ-AVI combined with COL was 0.312-1.000. Four isolates were synergistic, while the other 12 isolates were additive. Three isolates resistant to CAZ-AVI contained Class B resistance genes such as blaIMP and blaVIM, while 13 susceptible isolates carried resistance genes belonging to Class A, C or D. The logarithm values of mutation frequencies of drug resistance in CAZ-AVI group, COL group and combination group were -4.81±0.88, -7.06±0.69 and -9.70 (-9.78, -9.53), respectively. There were significant differences among the three groups (H = 33.601, P < 0.001), and between every two groups (adjusted P < 0.05). In time kill curves, the phytoplankton load of three XDR-PA decreased more than 6 log CFU/L when these two drugs were used together, and number of PA1819 planktonic bacteria decreased more than 5.1 log CFU/L compared with monotherapy group. Viable quantity in biofilm (A490) of normal saline group, CAZ-AVI group, COL group and CAZ-AVI-COL group were 0.665±0.068, 0.540±0.072, 0.494±0.642 and 0.317±0.080, respectively. There was significant difference between the other two groups (all P < 0.001), except for that between CAZ-AVI group and COL group (P = 0.109).
CONCLUSIONS:CAZ-AVI combined with COL can effectively improve the bactericidal effect of each drug alone on XDR-PA. The regimen can also reduce the production of drug-resistant bacteria and inhibit the formation of biofilm. Therefore, it is a potential treatment for XDR-PA infection.
