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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).

View this table: [in this window] [in a new window]   TABLE 1.   Polymyxin B-resistant isolate of Acinetobacter baumannii is sensitive to rBPI21 and to cecropin P1a

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

	REFERENCES

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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

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