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Antimicrobial Agents and Chemotherapy, March 2001, p. 994-995, Vol. 45, No. 3
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.994-995.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
LETTERS TO THE EDITOR
Polymyxin B-Resistant Acinetobacter baumannii
Clinical Isolate Susceptible to Recombinant BPI21
and Cecropin P1
 |
LETTER |
Many strains of Acinetobacter baumannii have become
resistant to a variety of clinically available antibacterial agents by both intrinsic and extrinsic mechanisms (4, 15). Several investigators have documented multidrug-resistant A. baumannii causing nosocomial infections and have demonstrated the
in vitro and in vivo activities of imipenem, sulbactam, and the
polymyxins (2, 9, 11, 14, 16). Increasing resistance to
antibacterials, including sulbactam and the carbapenems, has
prompted the use of polymyxin B and colistin as therapeutic
agents, and within the last several years, the polymyxins have been
used with increasing frequency to treat patients infected with
multidrug-resistant, gram-negative bacteria, including
Acinetobacter (9, 14, 16). Although the
literature, both clinical and microbiological, has shown that A. baumannii has retained susceptibility to the polymyxins despite
resistance to all other antibacterial agents (2, 15), we
document the isolation of a polymyxin B-resistant strain of A. baumannii from a patient who was given polymyxin B for treatment of a multidrug-resistant, polymyxin-susceptible strain of A. baumannii. The minimal inhibitory concentrations for the
polymyxin-resistant strain (L1) were 48 µg/ml (polymyxin B) and 128 µg/ml (colistin) as determined by E-test methodology (AB Biodisk
North America Inc., Piscataway, N.J.). More importantly, we have found
that this strain is susceptible in vitro to rBPI21
(Neuprex; XOMA Corporation, Berkeley, Calif.) (provided by S. Carroll),
a recombinant form of the N-terminal domain of the human
bactericidal/permeability-increasing protein (Table
1). This isolate was also susceptible to
cecropin P1 (Sigma, St. Louis, Mo.), an antibacterial peptide from pig intestine (3). The antibacterial effects of
rBPI21 and cecropin P1 were manifest both in conventional
MIC and minimal bactericidal concentration (MBC) assays with
Mueller-Hinton broth and in bactericidal assays with nutrient broth. In
the later type of assay, the antibacterial potency of
rBPI21, but not of cecropin P1, toward A. baumannii was further increased nearly 100-fold in the presence of
sublethal amounts of serum (data not shown).
The bactericidal and antiendotoxin properties of cationic membrane
active (poly)peptides are well known (5-7, 10, 12, 13).
The superior in vitro activity of rBPI21, the results of extensive preclinical testing in animal models, and the protein's apparent lack of immunogenicity and toxicity for human recipients have
encouraged therapeutic trials in settings where conventional antibiotics are unable to control infection by gram-negative bacteria and/or proinflammatory effects of endotoxin (1, 6, 8, 10).
Sublethal alterations of the gram-negative bacterial outer membrane in
combination with the use of antibiotics that, because of resistance,
are now ineffective alone may further extend therapeutic opportunities
(1, 7, 8). The activity of rBPI21 toward gram-negative bacteria with high levels of resistance to polymyxin B,
documented here for A. baumannii and previously observed
experimentally with several other species of gram-negative bacteria
(5, 7), illustrates additional important attributes that
may support its use as a therapeutic agent. Investigations of the
molecular bases of polymyxin B resistance in Acinetobacter
and other gram-negative bacteria and the activities of BPI and its
derivatives against these multidrug-resistant organisms are under way.
| |
ACKNOWLEDGMENTS |
These studies were supported in part by the BMA Medical
Foundation, the Beatrice Snyder Foundation, the Hugaton Foundation, and
Public Health Service grant DK05472.
| |
FOOTNOTES |
*
Phone: (718) 670-1525 Fax: (718)
661-7750 E-mail: cmurban{at}nyp.org
| |
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| | | | |
Carl Urban*
Noriel Mariano
James J. Rahal
Infectious Diseases Section
The New York Hospital
Medical Center of Queens
Flushing, New York
|
| | | | |
Emerald Tay
Conrado Ponio
Lutheran Medical
Center
Brooklyn, New York
|
| | | | |
Tomaz Koprivnjak
Inflammation Program
Department of
Microbiology
University of Iowa
Iowa City, Iowa
|
| | | | |
Jerrold Weiss
Inflammation
Program
Departments of Internal Medicine and
Microbiology
University of Iowa and
Iowa City Veterans'
Administration Medical Center
Iowa City,
Iowa
|
Antimicrobial Agents and Chemotherapy, March 2001, p. 994-995, Vol. 45, No. 3
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.994-995.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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