西太平洋地区出现多粘菌素异质性耐药的多重耐药鲍曼不动杆菌的临床分离株

David

Journal of Infection
Volume 58, Issue 2, February 2009, Pages 138-144

Colistin hetero-resistance in multidrug-resistant Acinetobacter baumannii clinical isolates from the Western Pacific region in the SENTRY antimicrobial surveillance programme

                               
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西太平洋地区出现多粘菌素异质性耐药的多重耐药鲍曼不动杆菌的临床分离株
Wing Yaua, Roxanne J. Owena, Anima Poudyala, Jan M. Bellb, c, John D. Turnidgeb, c, Heidi H. Yua, Roger L. Nationa,

                               
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,

                               
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and Jian Lia,

                               
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,

                               
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aFacility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
bDivision of Laboratory Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia
cUniversity of Adelaide, Adelaide, South Australia, Australia


Accepted 4 November 2008.  
Available online 6 December 2008.


SummaryBackgroundMultidrug-resistant Acinetobacter baumannii has presented a global medical problem. Emergence of colistin resistance, including hetero-resistance, has been increasingly reported. This study examined the susceptibility to colistin of multidrug-resistant A. baumannii from the Western Pacific region.
MethodsA total of 30 isolates were studied from 10 clinical centres in various countries. MICs were measured against 21 antibiotics by broth microdilution. Colistin population analysis profiles (PAPs) (0, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 mg/L) were determined. Time–kill kinetics of colistin against 3 isolates (2 colistin-susceptible (one of which was colistin hetero-resistant) and 1 colistin-resistant) were studied over a wide range of concentrations and development of resistance was monitored by measurement of colistin PAPs after 24-h exposure.
ResultsAll the isolates were highly multiresistant. Colistin MICs were 0.5–2 mg/L except one isolate which had an MIC of 128 mg/L. Seven isolates were colistin hetero-resistant with subpopulations growing at >2 mg/L. For the 2 colistin-susceptible isolates examined, >3log killing was observed within 3 h even at 0.5× MIC. Interestingly, >3log killing was also observed with the colistin-resistant isolate within 1 h even at 0.5 mg/L. Regrowth occurred at 24 h for both colistin-susceptible and -resistant isolates. Emergence of resistance to colistin after 24-h exposure was confirmed by PAP.
ConclusionColistin was very active against A. baumannii based upon MICs and initial killing in time–kill studies. Hetero-resistance in this group of A. baumannii isolates was less common than in previous studies. Nevertheless, care is required with colistin monotherapy for A. baumannii infections.

Keywords: Colistin; Acinetobacter baumannii; Hetero-resistance; Killing kinetics

David

b]文献复习

Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia. Jian.Li@vcp.monash.edu.au
Multidrug-resistant Acinetobacter baumannii has emerged as a significant clinical problem worldwide and colistin is being used increasingly as "salvage" therapy. MICs of colistin against A. baumannii indicate its significant activity. However, resistance to colistin in A. baumannii has been reported recently. Clonotypes of 16 clinical A. baumannii isolates and ATCC 19606 were determined by pulsed-field gel electrophoresis (PFGE), and colistin MICs were measured. The time-kill kinetics of colistin against A. baumannii ATCC 19606 and clinical isolate 6 were investigated, and population analysis profiles (PAPs) were conducted. Resistance development was investigated by serial passaging with or without exposure to colistin. Five different PFGE banding patterns were found in the clinical isolates. MICs of colistin against all isolates were within 0.25 to 2 microg/ml. Colistin showed early concentration-dependent killing, but bacterial regrowth was observed at 24 h. PAPs revealed that heteroresistance to colistin occurred in 15 of the 16 clinical isolates. Subpopulations (<0.1% from inocula of 10(8) to 10(9) CFU/ml) of ATCC 19606, and most clinical isolates grew in the presence of colistin 3 to 10 microg/ml. Four successive passages of ATCC 19606 in broth containing colistin (up to 200 microg/ml) substantially increased the proportion of the resistant subpopulations able to grow in the presence of colistin at 10 microg/ml from 0.000023 to 100%; even after 16 passages in colistin-free broth, the proportion only decreased to 2.1%. This represents the first demonstration of heterogeneous colistin-resistant A. baumannii in "colistin-susceptible" clinical isolates. Our findings give a strong warning that colistin-resistant A. baumannii may be observed more frequently due to potential suboptimal dosage regimens recommended in the product information of some products of colistin methanesulfonate.