Nemec, A.
Citation
Nemec, A. (2009, September 23). Antimicrobial resistance and clonality in Acinetobacter baumannii. Retrieved from https://hdl.handle.net/1887/14012
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/14012
Note: To cite this publication please use the final published version (if applicable).
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Resistance mechanisms in A. baumannii
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Cytoplasm
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Figure 1. General mechanisms of resistance to antimicrobial agents in Gram-negative bacteria.
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Table 1. Mechanisms of resistance of A. baumannii to clinically important antibiotics
Mechanism Typical resistance to Desription of the mechanism
responsible component ȕ-lactam hydrolysis
ADC* Cephalosporins† AmpC-type ȕ-lactamase intrinsic to A. baumannii TEM-1, CARB-5, SCO-1 Carboxypenicillins Narrow spectrum class A ȕ-lactamases VEB-1, PER*, TEM-92, CTX-M-2 Cephalosporins Broad spectrum class A ȕ-lactamases OXA-51* Carbapenems† Class D ȕ-lactamase intrinsic to A. baumannii OXA-23*, OXA-24*, OXA-58* Carbapenems Class D ȕ-lactamases
IMP*, VIM*, SIM-1 Carbapenems Metalo-ȕ-lactamases
Aminoglycoside modification
AAC(3)-Ia Gentamicin Ubiquitous acetyltransferase
AAC(3)-IIa Gentamicin, tobramycin Acetyltransferase AAC(6')-Ib, AAC(6')-Ih Tobramycin, amikacin Acetyltransferases
APH(3’)-I Kanamycin Ubiquitous phosphotransferase
APH(3’)-VI Amikacin Phosphotransferase typical for Acinetobacter spp.
ANT(2’’)-Ia Gentamicin, tobramycin Ubiquitous nucleotidyltransferase Target alteration
GyrA, ParC Quinolones Subunits DNA topoisomerases
ArmA Aminoglycosides 16 rRNA methylase
Active efflux
AdeABC Aminoglycosides† Chromosomally encoded nonspecific efflux pump Tet(A), Tet(B) Tetracyclines Tetracycline-specific efflux pumps
Changes in outer-membrane proteins
CarO Carbapenems Protein responsible for drug infflux
In addition to the above list, a number of resistance mechanisms and/or genes have been reported to occur in A. baumannii that have known or putative role in natural or acquired resistance of this species (Dijkshoorn et al. 2007, Peleg et al. 2008). Mechanisms so far identified in strains from the Czech Republic are underlined. *, Several allelic variants known; †, upregulation of the system necessary for resistant phenotype.
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Table 2. Published data on the origin of A. baumannii isolates related to EU clones I-III Isolates
related to Reference Country (year) of isolation Main method of
the clonal assigment Study
EU clone I Dijkshoorn et al. 1996 Belgium (1990), the Netherlands 8. ±
AFLP Comparison of European outbreak strains
Devaud et al. 1982 Switzerland (1977) AFLP* Genetic analysis of an outbreak strain Nemec et al. 2004
(= Chapter 2)
&]HFK5HSXEOLF ± $)/3 $FRXQWU\ZLGHUHWURVSHFWLYHVWXG\
van Dessel et al. 2004 Italy, Poland, Spain, South Africa DOO ±
AFLP Population analysis of European
fluoroquinolone-resistant isolates
Abbott et al. 2005 Ireland (2004) AFLP* Analysis of a horse isolate
Fournier et al. 2006 France (2002) AFLP*, Turton et al. 2007 Completelly sequenced strain AYE 7XUWRQHWDO 8. ± 7XUWRQHWDO (YDOXDWLRQRIDVHTXHQFHEDVHGPHWKRG
for identification of EU clones Nemec et al. 2007
(= Chapter 4)
Australia (> 1990), Bulgaria (2001), Hungary (1995)
AFLP Analysis of the AdeABC efflux in a diverse set of retrospective isolates
Nemec et al. 2008 (= Chapter 5)
&]HFK5HSXEOLF ± $)/3 $FRXQWU\ZLGHSURVSHFWLYHVWXG\
Towner et al. 2008 Bulgaria, Croatia, Estonia, Greece, Norway, Poland, 6ORYHQLD DOO±
Turton et al. 2007 Population analysis of European carbapanem-resistant isolates
Post & Hall 2009 Austraila (1997) Turton et al. 2007 Genetic analysis of a MDR strain '$UUH]RHWDO ,WDO\ ± 7XUWRQHWDO $QDO\VLVRILVRODWHVIURP,&8VLQ5RPH
EU clone II Dijkshoorn et al. 1996 Denmark (1984), the Netherlands (1982), UK (1989)
AFLP Comparison of European outbreak strains
Nemec et al. 2004 (= Chapter 2)
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van Dessel et al. 2004 France, Greece, Poland, Portugal, South Africa, Spain, Turkey (all
±
AFLP Population analysis of European
fluoroquinolone-resistant isolates
Bartual et al. 2004 Spain (1997, 2000-2002) MLST (Bartual et al. 2004) Evaluation of a MLST scheme 7XUWRQHWDO 8. ± 6SDLQ,VUDHO 7XUWRQHWDO 7KUHHVXEFORQHVRI(8FORQH,,IURP8.
Nemec et al. 2008 (= Chapter 5)
&]HFK5HSXEOLF ± $)/3 $FRXQWU\ZLGHSURVSHFWLYHVWXG\
Nemec et al. 2007 (= Chapter 4)
Bulgaria (1997), Hungary (1993) AFLP Analysis of the AdeABC efflux in a diverse set of retrospective isolates
Towner et al. 2008 Bulgaria, Czech Republic, Germany, Greece, Spain, Poland, Slovakia, UK
DOO±
Turton et al. 2007 Population analysis of European carbapanem-resistant isolates
Iacomo et al. 2008 Italy (2005) Turton et al. 2007 Completelly sequenced strain ACICU Whitman et al. 2008 USA (2006) PCR/ESI-MS (Ecker et al.
2006 )
Cause of pneumonia in a health care worker
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EU clone III van Dessel et al. 2004 Spain, the Netherlands, France, ,WDO\ DOO ±
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fluoroquinolone-resistant isolates +X\VHWDOD %HOJLXP ± 5HS3&5ILQJHSULQWLQJ
(Huys et al. 2005b)
Study on EU clone III
7XUWRQHWDO 8. ± 6SDLQ 7XUWRQHWDO (YDOXDWLRQRIDVHTXHQFHEDVHGPHWKRG
for identification of EU clones Nemec et al. 2007
(= Chapter 4)
The Netherlands (2000) AFLP Analysis of the AdeABC efflux in a diverse set of retrospective isolates
* Unpublished. Clonal assignment based on additional AFLP analysis performed in the Leiden University Medical Center.
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Figure 2. Geographic origin and the population structure of the in-detail studied isolates of A. baumannii from the Czech Republic. A. Results of 77 retrospective isolates from the period between 1991 and 1997 (Nemec et al. 1999, Chapter 2). B. Results of 108 prospective isolates of 2005-2006 (Chapter 5).
EU clone I EU clone II EU clones I&II Non EU clone I&II strains
1991-1997
2005-2006
EU clone II (n=66)
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EU clone I EU clone II EU clones I&II Non EU clone I&II strains
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61
Figure 3. Distribution of 108 A. baumannii clinical isolates from the Czech Republic according to the level of multidrug resistance and allocation to EU clones. The isolates were prospectively collected from as many as 56 ICUs in 20 hospitals in the period of 2005-2006 (for the geographical distribution of hospitals see Figure 2) (Chapter 5). The antimicrobials used were imipenem, meropenem, ceftazidime, piperacillin, ampicillin- VXOEDFWDP FLSURÀR[DFLQ JHQWDPLFLQ QHWLOPLFLQ DPLNDFLQ WREUDP\FLQ FRWULPR[D]ROH GR[\F\FOLQH DQG
colistin. The 33 fully susceptible isolates belonged to 25 different AFLP genotypes.
0.125 0.25 0.5 1 2 4 8 16
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Susceptible‡ 13/19 20/13 0/1 0/0 0/0 0/0 0/0 0/0 33
0.25 0.5 1 2 4 8 16 >16
Multidrug resistant 0 10 22 19 10 12 1 1 75
Susceptible 7 26 0 0 0 0 0 0 33
1 2 4 8 16 32 64 128
Multidrug resistant 8 21 8 6 7 2 4 19 75
Susceptible 23 11 0 0 0 0 0 0 33
* Intermediate and resistance values are highlighted
†Resistant to more than two antibiotics which are primarily effective against A. baumanni (see below).
‡ Susceptible to aminoglycosides, carbapenems, ofloxacin, doxycycline, ceftazidime and piperacillin.
Isolates
No. of isolates MIC for amikacin (mg/l)
Total Isolates
No. of isolates MIC for tobramycin (mg/l)
Total MIC for imipenem/meropenem (mg/l)*
Table 3. Distribution of minimal inhibitory concentration for carbapenems and
aminoglycosides in 108 A. baumannii isolates from the Czech Republic from 2005-2006.
Isolates
No. of isolates
Total
62
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63
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References
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±
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OHYHOFDUEDSHQHPUHVLVWDQFHLQA. baumanniiLVQRWGXHVROHO\WRWKHSUHVHQFHRIEHWDODFWDPDVHVJ Clin Microbiol ±
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6XVFHSWLELOLW\7HVWLQJ )LIWHHQWK,QIRUPDWLRQDO6XSSOHPHQW06&/6,:D\QH3$86$
Da Silva G, Dijkshoorn L, van der Reijden T et al. (2007),GHQWL¿FDWLRQRIZLGHVSUHDGFORVHO\
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RI PDMRU PXOWLUHVLVWDQW FORQHV RI Acinetobacter baumannii E\ PXOWLORFXV VHTXHQFH W\SLQJ Clin Microbiol Infect VXSSO 6
Dijkshoorn L, Aucken H, Gerner-Smidt P et al. (1996) &RPSDULVRQ RI RXWEUHDN DQG QRQRXWEUHDN
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Dijkshoorn L, Nemec A, Seifert H. (2007)$Q LQFUHDVLQJ WKUHDW LQ KRVSLWDOV PXOWLGUXJUHVLVWDQW
Acinetobacter baumanniiNat Rev Microbiol ±
Ecker JA, Massire C, Hall TA et al. (2006) ,GHQWL¿FDWLRQRIAcinetobacterVSHFLHVDQGJHQRW\SLQJRI
Acinetobacter baumanniiE\PXOWLORFXV3&5DQGPDVVVSHFWURPHWU\J Clin Microbiol ±
Fournier PE, Vallenet D, Barbe V et al. (2006) &RPSDUDWLYHJHQRPLFVRIPXOWLGUXJUHVLVWDQFHLQ
Acinetobacter baumanniiPLoS Genet H
Gerner-Smidt P, Tjernberg I, Ursing J. (1991).5HOLDELOLW\RISKHQRW\SLFWHVWVIRULGHQWL¿FDWLRQRI
AcinetobacterVSHFLHVJ Clin Microbiol ±
Héritier C, Poirel L, Nordmann P. (2006) &HSKDORVSRULQDVHRYHUH[SUHVVLRQUHVXOWLQJIURPLQVHUWLRQ
RI,6Aba1 in Acinetobacter baumanniiClin Microbiol Infect ±
Hujer KM, Hujer AM, Hulten EA et al. (2006) $QDO\VLVRIDQWLELRWLFUHVLVWDQFHJHQHVLQPXOWLGUXJ
resistant AcinetobacterVSLVRODWHVIURPPLOLWDU\DQGFLYLOLDQSDWLHQWVWUHDWHGDWWKH:DOWHU5HHG$UP\
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