Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China.
BACKGROUND
The clonal spread of Acinetobacter baumannii is a global problem, and carbapenems, such as imipenem, remain the first-choice agent against A. baumannii. Using synergy to enhance the antibiotic activity of carbapenems could be useful. Here, amlodipine (AML) was tested alone and with imipenem against A. baumannii isolates.


METHODS
Forty-two isolates of A. baumannii were collected. Multilocus sequence typing (MLST) assessed the genetic relationship of the isolates. The resistance phenotypes were determined using disc diffusion. The minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution. The combined effects of the drugs were determined by a checkerboard procedure. Metallo-β-lactamase (MBL) was determined using the MBL Etest.


RESULTS
Forty-two A. baumannii isolates were collected from 42 patients who were mostly older than 65 years and had long inpatient stays (≥ 7 days). A. baumannii was mostly recovered from the respiratory system (N = 35, 83.3%). Most patients (N = 27, 64.3%) received care in intensive care units (ICUs). Disc diffusion testing demonstrated that A. baumannii susceptibility to polymyxin B was 100%, while susceptibility to other antimicrobial agents was less than 30%, classifying the isolates into 10 MDR and 32 XDR strains. MLST grouped the A. baumannii isolates into 4 existing STs and 6 new STs. STn4 carried allele G1, with a T → C mutation at nt3 on the gpi111 locus. STn5 carried allele A1, possessing A → C mutations at nt156 and nt159 on the gltA1 locus. ST195 and ST208 accounted for 68.05% (29/42) of the isolates. Clonal relation analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. The inhibitory concentration of imipenem ranged from 0.5 to 32 μg/ml, and that of AML ranged from 40 to 320 μg/ml. In combination, the susceptibility rate of A. baumannii isolates increased from 16.7% to 54.8% (P = 0.001). In the checkerboard procedure, half of the isolates (N = 21, 50.0%) demonstrated synergy or partial synergy with the drug combination. The MBL Etest revealed that 1 A. baumannii strain (N = 1, 2.4%) produced MBL.


CONCLUSIONS
CC92 was the major clone spreading in our hospital. AML improved the activity of imipenem against A. baumannii isolates in vitro but did not inhibit MBL.
Yu jun
Yj
Li
Chu zhi
Cz
Pan
Department of Respiratory Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, Panfu Road, Guangzhou, China. zhaozw@yeah.net.
Zi wen
Zw
Zhao
Zhu xiang
Zx
Zhao
Hui ling
Hl
Chen
Wei bo
Wb
Lu
D000151:Acinetobacter Infections / Q000453:epidemiology / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D000368:Aged; D017311:Amlodipine / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002681:China / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
D000900:Anti-Bacterial Agents; D017311:Amlodipine; D015378:Imipenem; D001618:beta-Lactamases