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Antimicrobial Agents and Chemotherapy, October 2005, p. 4425-4426, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4425-4426.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Antibiotic Susceptibility of Stenotrophomonas maltophilia in the Presence of Lactoferrin


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LETTER
 
Stenotrophomonas maltophilia is resistant to most antibiotics and infects the respiratory tract of cystic fibrosis (CF) patients (5). CF sputum contains a high concentration of lactoferrin (0.9 mg/ml) (9). Lactoferrin damages outer membranes of gram-negative bacteria (6), which might explain why MICs for Pseudomonas aeruginosa of rifampin and chloramphenicol were reduced in the presence of 0.9 mg/ml of human lactoferrin (7). Colistin (8) and other agents (4) that increase outer membrane permeability of gram-negative bacteria have enhanced the susceptibility of S. maltophilia to rifampin. As potentiation of antibiotic activity by lactoferrin may influence treatment of CF infections, we investigated the effect of lactoferrin (0.9 mg/ml) on susceptibilities of CF S. maltophilia isolates to drugs used to treat S. maltophilia infections (ceftazidime, gentamicin, trimethoprim, and rifampin). Lactoferrin enhanced the sensitivity of P. aeruginosa (7) to chloramphenicol, so we looked for similar effects with S. maltophilia.

Clinical isolates of S. maltophilia were from Booth Hall Hospital, Manchester, United Kingdom. Human recombinant lactoferrin was from Agennix Inc., Houston, Tex.; rifampin and chloramphenicol were from Mast Laboratories, United Kingdom; gentamicin sulfate from Sigma; ceftazidime pentahydrate was from GlaxoSmithKline; and trimethoprim was from APS-Berk, Sussex, United Kingdom.

Determination of MICs with and without 0.9 mg/ml lactoferrin was by broth microdilution (7) including antibiotic-free controls with and without lactoferrin. Bacterial suspensions were diluted to a final concentration of 105 CFU/ml. The minimum bactericidal concentration (MBC) was the concentration that led to 99.9% killing.

For each MIC and MBC, eight replicate tests were performed, and results are presented as medians. Analysis was by Mann-Whitney U test.

Rifampin MICs (Table 1) for all isolates were lower (2- to 16-fold) with lactoferrin than without, while the rifampin MBCs were lowered 2- to 4-fold in the presence of lactoferrin (P < 0.001 for all isolates). For two out of the three isolates tested for gentamicin sensitivity, median MICs and MBCs were significantly lower with lactoferrin. All MICs and MBCs of chloramphenicol and trimethoprim (four isolates tested) and MICs of ceftazidime (three isolates tested) were within the tested ranges and were not lower with lactoferrin (data not shown). MBCs of ceftazidime for two of the isolates were above the tested range (>256 µg/ml), and those for the remaining strains were unchanged on addition of lactoferrin. All isolates were resistant to trimethoprim (MICs, 64 to 256 µg/ml).


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  		TABLE 1. Median MICs and MBCs (µg/ml) of rifampin and gentamicin for clinical isolates (eight replicates per isolate) of S. maltophilia with (+LF) and without (–LF) lactoferrin (0.9 mg/ml)

Rifampin MBCs for S. maltophilia were lower with lactoferrin, as were MICs which fell from levels that are not clinically obtainable to 12 µg/ml or below (levels that have been recorded in the sputum of some rifampin-treated patients) (1). This finding supports use of rifampin in treatment of S. maltophilia infections of CF patients. Our findings with rifampin concur with reports of similar effects with other gram-negative bacteria, such as Burkholderia cepacia (2) and mucoid P. aeruginosa isolates from CF patients (2, 7), Escherichia coli (3, 6), and Salmonella enterica serovar Typhimurium (10). In contrast to S. enterica serovar Typhimurium (10) and P. aeruginosa (7), susceptibility of S. maltophilia to chloramphenicol was not enhanced by lactoferrin. These and previous findings (2, 7) suggest that for CF respiratory infections, it may be more appropriate to test antibiotic sensitivities in the presence of lactoferrin.


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  1. Acocella, G. 1983. Pharmacokinetics and metabolism of rifampin in humans. Rev. Infect. Dis. 5(Suppl. 3):428-432.
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  2. Alkawash, M., M. Head, and J. S. Soothill. 1999. MICs of doxycycline and rifampicin for Burkholderia cepacia and Pseudomonas aeruginosa strains are lower in the presence of human lactoferrin. J. Antimicrob. Chemother. 44:385-387.[Abstract/Free Full Text]
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  3. Chen, P. W., S. P. Ho, C. L. Shyu, and F. C. Mao. 2004. Effect of bovine lactoferrin hydrolysate on the in vitro antimicrobial susceptibility of Escherichia coli strains isolated from baby pigs. Am. J. Vet. Res. 65:131-137.[CrossRef][Medline]
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  4. Denny, B., P. West, and D. Panigrahi. 2003. Effects of permeabilizers on antimicrobial susceptibility of Stenotrophomonas maltophilia and Acinetobacter spp. J. Microbiol. Immunol. Infect. 31:72-76.
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  5. Denton, M. 1997. Stenotrophomonas maltophilia: an emerging problem in cystic fibrosis patients. Rev. Med. Microbiol. 8:15-19.
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  6. Ellison, R. T., T. J. Ghiel, and F. M. LaForce. 1988. Damage to the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin. Infect. Immun. 56:2774-2781.[Abstract/Free Full Text]
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  7. Fowler, C. E., J. S. Soothill, and L. Oakes. 1997. MICs of rifampicin and chloramphenicol for mucoid Pseudomonas aeruginosa strains are lower when human lactoferrin is present. J. Antimicrob. Chemother. 40:877-879.[Abstract/Free Full Text]
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  8. Giamarellos-Bourboulis, E. J., L. Karnesis, and H. Giamarellou. 2002. Synergy of colistin with rifampin and trimethoprim/sulfamethoxazole on multidrug-resistant Stenotrophomonas maltophilia. Diagn. Microbiol. Infect. Dis. 44:259-263.[CrossRef][Medline]
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  9. Jacquot, J., J. M. Tournier, T. G. Carmona, E. Puchelle, J. P. Chazalett, and E. Sadoul. 1983. Proteins of bronchial secretions in mucoviscidosis. Role in infection. Bull. Eur. Physiopathol. Respir. 19:453-459. (In French.)[Medline]
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  10. Naidu, A. S., and R. R. Arnold. 1994. Lactoferrin interaction with salmonellae potentiates antibiotic susceptibility in vitro. Diagn. Microbiol. Infect. Dis. 20:69-75.[CrossRef][Medline]
Ahmed O. Qamruddin
Department of Microbiology
2nd Floor Clinical Sciences Building
Manchester Royal Infirmary
Oxford Road
Manchester, M13 9WL, United Kingdom

Mustafa A. Alkawash
James S. Soothill*
Infectious Diseases and Microbiology Unit
Institute of Child Health
30 Guilford Street
University College
London, WC1N 1EP, United Kingdom,1

* Phone: 44 207 405 9200, ext. 5237, Fax: 44 207 813 8268, E-mail: soothj{at}gosh.nhs.uk

Antimicrobial Agents and Chemotherapy, October 2005, p. 4425-4426, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4425-4426.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Caraher, E. M., Gumulapurapu, K., Taggart, C. C., Murphy, P., McClean, S., Callaghan, M. (2007). The effect of recombinant human lactoferrin on growth and the antibiotic susceptibility of the cystic fibrosis pathogen Burkholderia cepacia complex when cultured planktonically or as biofilms. J Antimicrob Chemother 60: 546-554 [Abstract] [Full Text]  

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