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LETTERS TO THE EDITOR

Antibiotic Susceptibility of Stenotrophomonas maltophilia in the Presence of Lactoferrin

Ahmed O. Qamruddin, Mustafa A. Alkawash, James S. Soothill
Ahmed O. Qamruddin
Department of Microbiology 2nd Floor Clinical Sciences Building Manchester Royal Infirmary Oxford Road Manchester, M13 9WL, United Kingdom
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Mustafa A. Alkawash
1Infectious Diseases and Microbiology Unit Institute of Child Health 30 Guilford Street University College London, WC1N 1EP, United Kingdom
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James S. Soothill
1Infectious Diseases and Microbiology Unit Institute of Child Health 30 Guilford Street University College London, WC1N 1EP, United Kingdom
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  • For correspondence: soothj@gosh.nhs.uk
DOI: 10.1128/AAC.49.10.4425-4426.2005
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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).

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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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)

  • Copyright © 2005 American Society for Microbiology

REFERENCES

  1. 1.↵
    Acocella, G. 1983. Pharmacokinetics and metabolism of rifampin in humans. Rev. Infect. Dis.5(Suppl. 3):428-432.
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    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.
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    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.
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    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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    Denton, M. 1997. Stenotrophomonas maltophilia: an emerging problem in cystic fibrosis patients. Rev. Med. Microbiol.8:15-19.
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  6. 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.
    OpenUrlAbstract/FREE Full Text
  7. 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.
    OpenUrlCrossRefPubMedWeb of Science
  8. 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.
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  9. 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.)
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    Naidu, A. S., and R. R. Arnold. 1994. Lactoferrin interaction with salmonellae potentiates antibiotic susceptibility in vitro. Diagn. Microbiol. Infect. Dis.20:69-75.
    OpenUrlCrossRefPubMedWeb of Science
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Antibiotic Susceptibility of Stenotrophomonas maltophilia in the Presence of Lactoferrin
Ahmed O. Qamruddin, Mustafa A. Alkawash, James S. Soothill
Antimicrobial Agents and Chemotherapy Sep 2005, 49 (10) 4425-4426; DOI: 10.1128/AAC.49.10.4425-4426.2005

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Antibiotic Susceptibility of Stenotrophomonas maltophilia in the Presence of Lactoferrin
Ahmed O. Qamruddin, Mustafa A. Alkawash, James S. Soothill
Antimicrobial Agents and Chemotherapy Sep 2005, 49 (10) 4425-4426; DOI: 10.1128/AAC.49.10.4425-4426.2005
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KEYWORDS

Anti-Bacterial Agents
Gram-negative bacterial infections
lactoferrin
Stenotrophomonas maltophilia

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