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Antimicrobial Agents and Chemotherapy, February 1999, p. 213-217, Vol. 43, No. 2
Service de Microbiologie, Hôpital
Robert Debré, 75019 Paris, France
Received 12 May 1998/Returned for modification 26 August
1998/Accepted 27 October 1998
We evaluated the activities of meropenem, imipenem, temocillin,
piperacillin, and ceftazidime by determination of the MICs for 66 genotypically characterized Burkholderia cepacia isolates obtained from the sputum of cystic fibrosis patients. In vitro synergy
assays, as performed by the time-kill methodology, of two- and
three-drug combinations of the Burkholderia cepacia, a
phytopathogen first described in the 1950s (16), can cause
opportunistic and nosocomial infections. When recovered from the sputum
of cystic fibrosis (CF) patients, it is associated with a poor clinical
prognosis, because fatal pulmonary infections occur in approximately
20% of colonized patients (16, 39). Isolates associated
with acute clinical decline belong to genomovar III (42).
B. cepacia is resistant to many of the traditional
antipseudomonal antibiotics, and concomitant use of two or more drugs
is often necessary to eradicate B. cepacia from CF patients.
Meropenem is a novel carbapenem antibiotic with good activity against
B. cepacia (26, 33). In our study, we compared
its efficacy against strains isolated from the sputum of CF patients with those of the antipseudomonal Bacterial strains.
Ninety-five previously described
(36) clinical B. cepacia isolates were studied.
They were recovered from the sputum of 71 CF patients attending 13 French care centers located in nine regions from April 1988 to April
1995. The identities of the isolates were confirmed by standard
biochemical procedures (API 20 NE; BioMérieux, Marcy l'Etoile, France).
Genotypic analysis.
Genotypic characterization was based on
the analysis of ribosomal DNA regions (ribotyping) with
EcoRI as described previously (4, 5).
Antimicrobial agents.
Susceptibility to the following
antibiotics was tested: piperacillin, ceftazidime, imipenem, meropenem,
temocillin, sulbactam, ciprofloxacin, rifampin,
trimethoprim-sulfamethoxazole (TMP-SMZ), minocycline, and tobramycin.
Susceptibility testing. (i) Antibiotic susceptibility
pattern.
Antibiotic susceptibility patterns were determined by the
disk diffusion method according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria (29, 31).
Mueller-Hinton plates (Pasteur Diagnostic, Marnes la Coquette, France)
were inoculated with a 0.5 McFarland standard suspension of organisms,
and disks (Pasteur Diagnostic) were applied. Zones of growth inhibition were recorded in millimeters after overnight incubation at 35°C.
(ii) MIC determinations.
The antibiotics were obtained from
the manufacturers as powders suitable for susceptibility testing. MICs
were determined by the dilution method on Mueller-Hinton agar plates as
recommended by NCCLS (30). The replicator prong delivered
approximately 104 CFU per spot. The MIC50 and
MIC90 were defined as the concentrations at which 50 and
90% of the strains were inhibited, respectively. NCCLS breakpoints for
nonmembers of the family Enterobacteriaceae were used to
define susceptibility to all drugs except temocillin and rifampin, for
which there are no NCCLS recommendations (31). For
temocillin and rifampin we used the breakpoints recommended by Fuchs et
al. (14) and the Comité de l'Antibiogramme de la Société Française de Microbiologie (12),
respectively. To avoid duplication, the MIC determination was not
repeated when a strain with an identical ribotype and antibiotic
susceptibility pattern was isolated twice in the same care center.
Synergy and killing activities.
The synergy and killing
activities of the drugs against 10 strains were determined. The 10 strains were genotypically unrelated on the basis of their ribotypes
and antibiotic susceptibility patterns. Microtiter plates (Consortium
de Matériel pour Laboratoires, Nemours, France) were used to
perform the synergy assays and to determine the killing activities for
these 10 strains, as described previously (13, 43, 44). A
24-h incubation period with an exponential-phase culture adjusted to
approximately 105 CFU/ml in Mueller-Hinton broth with
calcium and magnesium concentrations adjusted to 20 and 10 µg/ml,
respectively, was used. Each
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Comparative In Vitro Activities of Meropenem, Imipenem,
Temocillin, Piperacillin, and Ceftazidime in Combination with
Tobramycin, Rifampin, or Ciprofloxacin against Burkholderia
cepacia Isolates from Patients with Cystic Fibrosis
ABSTRACT
Top
Abstract
Introduction
Materials and methods
Results
Discussion
References
-lactams with tobramycin, rifampin,
and/or ciprofloxacin were also performed with 10 strains susceptible,
intermediate, or resistant to fluoroquinolones. On the basis of the
MICs, meropenem and temocillin were the most active -lactam agents,
with MICs at which 90% of isolates are inhibited of 8 and 32 µg/ml,
respectively. The addition of ciprofloxacin significantly enhanced the
killing activities of piperacillin, imipenem, and meropenem against the
10 strains tested (P < 0.05). The best killing
activity was obtained with the combination of meropenem and
ciprofloxacin, with bactericidal activity of 3.31 ± 0.36 log10 CFU/ml (P < 0.05). Compared to the
activity of the two-drug -lactam-ciprofloxacin combination, the
addition of rifampin or tobramycin did not significantly increase the
killing activity (P > 0.05). The three-drug
combinations (with or without ciprofloxacin) significantly enhanced the
killing activities of piperacillin, imipenem, and meropenem relative to
the activities of the -lactams used alone (P < 0.05). The combination -lactam-ciprofloxacin-tobramycin was
the combination with the most consistently synergistic effect.
INTRODUCTION
Top
Abstract
Introduction
Materials and methods
Results
Discussion
References
-lactam agents temocillin, piperacillin, ceftazidime, and imipenem. The MICs and in vitro synergy,
as determined by the time-kill methodology, of two- and three-drug
combinations of the -lactams with tobramycin, rifampin, and/or
ciprofloxacin against genotypically characterized B. cepacia isolates were determined.
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and methods
Results
Discussion
References
-lactam agent was tested alone and in
two- and three-drug combinations with ciprofloxacin, tobramycin, or
rifampin. The antibiotics were assessed for their synergistic effects
and killing activities at 0.5 and 1× the MIC, respectively; these
concentrations are close to the usual concentrations found in sputum
(15, 19, 20, 25, 41). However, because the MICs of imipenem,
rifampin, tobramycin, and ciprofloxacin (to which the strains are
resistant) for B. cepacia are far higher than the achievable
concentrations in sputum, we used imipenem, rifampin, and ciprofloxacin
concentrations of 2 µg/ml and a tobramycin concentration of 1 µg/ml
to approach the levels achieved in sputum (19, 23, 37, 38).
Viability counts were made at 24 h by plating 50 µl from each
well onto chocolate agar plates with a Spiral plater (Spiral Systems
Inc., Cincinnati, Ohio). The numbers of viable bacteria were counted by
the Spiral Systems quadrant counting method after 24 h of
incubation at 37°C in room air. The detection limit was 20 CFU/ml.
Given the drug concentrations used, significant antibiotic carryover could be ruled out (45).
-lactam antibiotics and ciprofloxacin at a
frequency of about 10
6 at a concentration of 1× the MIC,
and regrowth in the assay wells prevented the detection of antibiotic
activity. Thus, an inoculum of 105 CFU/ml was used to
assess the killing activity synergies of the various combinations of
antibiotics. Moreover, to confirm that bacterial growth after 24 h
of incubation was not due to the selection of resistant mutants, the
susceptibilities of viable bacteria were compared with those of the
initial strains (which were redetermined at the same time) by the disk
diffusion method according to NCCLS criteria (29). When a
significant reduction in the diameter of the inhibition zone (
4 mm)
was observed, survivors were considered to be resistant mutants and the
killing activity results were not recorded. Indeed, preliminary
experiments showed that the mean standard deviation of the inhibition
zone diameter was 4 mm for a given strain when the disk diffusion test
was repeated 10 times.
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RESULTS |
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Top
Abstract
Introduction
Materials and methods
Results
Discussion
References
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Ribotyping generated 32 different patterns for the 95 clinical isolates; 29 isolates were considered duplicates and the MICs for those isolates were not determined.
The MICs of the antibiotics tested and the percentage of susceptible
strains among the remaining 66 isolates are reported in Table
1. Among the -lactam agents,
temocillin and meropenem had the best inhibitory activities, with 82 and 67% of strains being susceptible to the two drugs, respectively
(MIC90, 32 and 8 µg/ml, respectively). Among the non
-lactam agents, TMP-SMZ and minocycline had the best antimicrobial
activities, with 62 and 47% of strains being susceptible, respectively
(MIC90s, 8/152 and 64 µg/ml, respectively).
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The synergistic effects and killing activities of the antibiotics alone
and in combination were determined with 10 strains distinguished by
their ribotypes and antibiotic susceptibility patterns. The 10 strains
used were all susceptible to the -lactam agents tested (except for
imipenem). Preliminary experiments showed that the use of resistant
strains resulted in their growth in the assay well and prevented the
detection of antibiotic activity at clinically achievable
concentrations in sputum. The ranges of MICs for the 10 strains were as
follows: piperacillin, 2 to 16 µg/ml; ceftazidime, 1 to 4 µg/ml;
imipenem, 8 to 32 µg/ml; meropenem, 1 to 4 µg/ml; and temocillin, 2 to 8 µg/ml. Seven strains were susceptible or intermediate to
ciprofloxacin, with MICs ranging from 1 to 2 µg/ml. Synergistic
effects and killing activities, determined at 0.5 and 1× the MIC,
respectively, are reported in Fig. 1 and
Table 2, respectively.
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The effects of two-drug combinations comprising a -lactam agent (at
0.5× the MIC) and ciprofloxacin, rifampin, or tobramycin were
synergistic against 30 to 62%, 0 to 10%, and 0 to 37% of the
strains, respectively (Fig. 1). The two-drug combination observed to
have the most synergistic effect was ceftazidime-ciprofloxacin. At 1×
the MIC (Table 2), the maximal fall in bacterial counts was 1.14 log10 CFU/ml with the -lactams tested alone. The
addition of ciprofloxacin significantly enhanced the mean killing
activities of piperacillin, imipenem, and meropenem against the 10 tested strains (P < 0.05). The best killing activity
at 1× the MIC was obtained with the combination of meropenem and
ciprofloxacin, with bactericidal activity of 3.31 ± 0.36 log10 CFU/ml (P < 0.05). However, the
addition of ciprofloxacin to the -lactams did not enhance their
killing activities against the three fluoroquinolone-resistant strains
(MICs, 32 to 64 µg/ml) except in the cases of meropenem and
piperacillin, which caused decreases of 2.7 ± 0 and 1.9 ± 1.55 log10 CFU/ml, respectively. The addition of tobramycin
or rifampin did not enhance the killing activities against any of the
strains compared to those of the -lactams alone (P > 0.05).
The three-drug -lactam-tobramycin-rifampin combinations showed
synergistic effects against 0 to 33% of the strains. A greater synergistic effect (30 to 80% of strains) was obtained with the -lactam-ciprofloxacin-rifampin or
-lactam-ciprofloxacin-tobramycin combinations (Fig. 1). The
combination of -lactams (except imipenem) with ciprofloxacin and
tobramycin was the one with the most consistently synergistic effects
(against more than 60% of the strains). The addition of tobramycin to
the combination of meropenem or temocillin plus rifampin did not result
in a greater synergistic effect (Fig. 1).
Compared to the two-drug -lactam-ciprofloxacin combination, the
addition of rifampin or tobramycin did not significantly increase the
mean killing activity (P > 0.05) when 1× the MIC was
used (Table 2). The three-drug combinations at 1× the MIC (with or
without ciprofloxacin) significantly enhanced the killing activities of
piperacillin, imipenem, and meropenem relative to those of the
-lactams used alone (P < 0.05). The killing
activity of ceftazidime combined with ciprofloxacin and rifampin or
tobramycin was significantly superior to that of ceftazidime alone
(P < 0.05). In contrast, the killing activity of
temocillin in any of the two- or three-drug combinations was not
significantly enhanced (P > 0.05).
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DISCUSSION |
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Top
Abstract
Introduction
Materials and methods
Results
Discussion
References
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The multiple-antibiotic resistance of B. cepacia has
been attributed to an impermeable selective outer membrane (1, 28, 32), an efflux pump mechanism (7), and/or the
production of an inducible chromosomal -lactamase (3,
34). Given the reported spread of epidemic strains (17, 33,
36), we determined the MICs for all the strains that were
isolated from patients within the same care center and that had
different ribotypes and/or antibiotic susceptibility patterns. The MICs
observed in our study are consistent with those reported elsewhere for
all the drugs tested except sulbactam (10, 21, 26, 27, 33,
44). Contrary to Jacoby and Sutton (21), we found that
sulbactam was poorly active, with MIC50s above 64 µg/ml,
possibly because we tested isolates from CF patients. On the basis of
the MICs, temocillin and meropenem were the most active -lactam
agents, with no cross-resistance with imipenem, in agreement with Lewin et al. (26) and Pitt et al. (33). Meropenem also
had the narrowest MIC range. This may be explained by its recent
introduction in France. However, the long-term impact of meropenem use
on resistance rates among B. cepacia is unknown. The other
antibacterial agents used to treat CF patients, such as piperacillin,
ceftazidime, imipenem, and ciprofloxacin, had wider MIC ranges,
probably because of the emergence of resistant mutants in vivo. This
has been documented with Pseudomonas aeruginosa (15,
18) but may also occur with B. cepacia, because the
migration of insertion sequences within the chromosome can affect the
expression of genes that modulate antibiotic resistance
(35).
Previous studies have shown the value of antibiotic combinations such
as -lactam-ciprofloxacin, -lactam-ciprofloxacin-rifampin, and
-lactam-aminoglycoside against B. cepacia (2, 6,
10, 24, 27) and -lactam-aminoglycoside-rifampin against
P. aeruginosa (46, 47). We therefore tested the
activities of two- and three-drug combinations of these antibiotics
against our strains. Among the aminoglycosides, we chose tobramycin,
the MICs of which are lower than those of gentamicin and amikacin
(27, 33). The antibiotics were tested at 0.5 and 1× the
MICs to improve the detection of synergy (13) and to reflect
clinical conditions. Except for imipenem, rifampin, tobramycin, and
ciprofloxacin (to which strains were resistant), the achievable
concentrations in sputum were close to the relevant MICs (15, 19,
20, 23, 25, 37, 38, 41).
The potential of the use of -lactam-ciprofloxacin combinations
against B. cepacia has been investigated previously (6, 24, 27). Most of the latter studies were based on fractional inhibitory concentration indexes and gave variable results. In this
study, which was based on the time-kill method, the addition of
ciprofloxacin significantly increased the killing activities of
piperacillin and meropenem and, to a lesser extent, that of imipenem
against all strains susceptible or intermediate to fluoroquinolones. The synergistic effect of such combinations was superior to that of
-lactam combinations with aminoglycosides or rifampin. The results
are consistent with those of Kumar et al. (24) but are in
disagreement with those of Lu et al. (27); those
investigators tested imipenem plus rifampin or ciprofloxacin and
ceftazidime plus ciprofloxacin or amikacin, respectively. The
discrepancies may be explained by the origins of the strains (isolates
from CF patients in the study of Kumar et al. [24] and
invasive strains in the work of Lu et al. [27]) and by
the methodology used to detect synergistic effects. Indeed, no
correlation between the results obtained by the killing curve method
used by Kumar et al. (24) and the results obtained by the
checkerboard method used by Lu et al. (27) has been reported
(9). However, synergy is best detected by the time-kill
methodology, which is more able to predict the outcome of antibiotic
treatment (22).
A bactericidal effect was achieved by adding meropenem to ciprofloxacin. However, with the three ciprofloxacin-resistant strains tested, the decrease was less than 3 log10 CFU/ml.
Clinical trial data on the eradication of B. cepacia from CF patients are highly limited (8, 11, 15, 18, 40). Published results from trials involving small numbers of patients suggest a potential value of temocillin and the disappointing activity of ceftazidime (15, 40). The two- and three-drug combinations proposed in our study and the use of meropenem may be of interest in this setting. Clinical trials are required to corroborate our in vitro data.
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ACKNOWLEDGMENTS |
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We are indebted to O. Bajolet-Laudinat, Reims, France; G. Berthelot, Dieppe, France; J. Carrère, Giens, France; G. Chabanon, Toulouse, France; C. de Champs, Clermont-Ferrand, France; P. Honderlick, Suresnes, France; G. Paul, Paris, France; D. Tande, Brest, France; J. Texier-Maugein, Pessac, France; J. Thubert, Roscoff, France; H. Vu Thien, Paris; and M. Weber, Nancy, France, for providing strains and to A. Munck and J. Navarro, Paris, for helpful discussion.
This work was supported by a grant from the Association Française de Lutte contre la Mucoviscidose, 1995.
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FOOTNOTES |
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* Corresponding author. Mailing address: Service de Microbiologie, Hôpital R. Debré, 48 Bd Sérurier, 75019 Paris, France. Phone: 33 (1) 40 03 23 40. Fax: 33 (1) 40 03 24 50. E-mail: edouard.bingen{at}rdb.ap-hop-paris.fr.
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REFERENCES |
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Abstract
Introduction
Materials and methods
Results
Discussion
References
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| 1. |
Aronoff, S. C.
1988.
Outer membrane permeability in Pseudomonas cepacia diminished porin content in a -lactam-resistant mutant and in resistant cystic fibrosis isolates.
Antimicrob. Agents Chemother.
32:1636-1639 |
| 2. |
Aronoff, S. C., and J. Klinger.
1984.
In vitro activities of aztreonam, piperacillin, and ticarcillin with amikacin against amikacin-resistant Pseudomonas aeruginosa and Pseudomonas cepacia isolates from children with cystic fibrosis.
Antimicrob. Agents Chemother.
25:279-280 |
| 3. |
Beckman, W., and T. G. Lessie.
1980.
Multiple forms of Pseudomonas cepacia -lactamase, abstr. K-128, p. 148.
In
Abstracts of the 80th Annual Meeting of the American Society for Microbiology 1980. American Society for Microbiology, Washington, D.C.
|
| 4. |
Bingen, E. H.,
E. Denamur, and J. Elion.
1994.
use of ribotyping in epidemiological surveillance of nosocomial outbreaks.
Clin. Microbiol. Rev.
7:311-327 |
| 5. |
Bingen, E. H.,
M. Weber,
J. Derelle,
N. Brahimi,
N. Y. Lambert-Zechovsky,
M. Vidailhet,
J. Navarro, and J. Elion.
1993.
Arbitrarily primed polymerase chain reaction as a rapid method to differentiate crossed from independent Pseudomonas cepacia infections in cystic fibrosis patients.
J. Clin. Microbiol.
31:2589-2593 |
| 6. |
Bosso, J. A.,
B. A. Saxon, and J. M. Matsen.
1990.
In vitro activities of combinations of aztreonam, ciprofloxacin, and ceftazidime against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.
Antimicrob. Agents Chemother.
34:487-488 |
| 7. | Burns, J. L., C. D. Wadsworth, J. J. Barry, and C. P. Goodall. 1996. Nucleotide sequence analysis of a gene from Burkholderia (Pseudomonas) cepacia encoding an outer membrane lipoprotein involved in multiple antibiotic resistance. Antimicrob. Agents Chemother. 40:307-313[Abstract]. |
| 8. | Byrne, S., J. Maddison, P. Connor, I. Doughty, M. Jenney, A. K. Webb, and T. J. David. 1995. Clinical evaluation of meropenem versus ceftazidime for the treatment of Pseudomonas spp. infections in cystic fibrosis patients. J. Antimicrob. Chemother. 36(Suppl. A):135-143. |
| 9. | Cappellety, D. M., and M. J. Rybak. 1996. Comparison of methodologies for synergism testing of drug combinations against resistant strains of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 40:677-683[Abstract]. |
| 10. | Chin, N. X., and H. C. Neu. 1989. Synergy of new C-3 substituted cephalosporins and tobramycin against Pseudomonas aeruginosa and Pseudomonas cepacia. Diagn. Microbiol. Infect. Dis. 12:343-349[Medline]. |
| 11. |
Ciofu, O.,
T. Jensen,
T. Pressler,
H. K. Johansen,
C. Koch, and N. Hoiby.
1996.
Meropenem in cystic fibrosis patients infected with resistant Pseudomonas aeruginosa or Burkholderia cepacia and with hypersensitivity to -lactams antibiotics.
Clin. Microbiol. Infect.
2:91-98.
[Medline] |
| 12. | Comité de l'Antibiogramme de la Société Française de Microbiologie. 1997. Communiqué 1997. Pathol. Biol. 45:1-12. |
| 13. | Eliopoulos, G. M., and R. C. Moellering, Jr. 1996. Antimicrobial combinations, p. 330-396. In V. Lorian (ed.), Antibiotics in laboratory medicine, 4th ed. The Williams & Wilkins Co., Baltimore, Md. |
| 14. | Fuchs, P. C., A. L. Barry, C. Thornsberry, and R. N. Jones. 1985. Interpretive criteria for temocillin disk diffusion susceptibility testing. Eur. J. Clin. Microbiol. 4:30-33[Medline]. |
| 15. | Gold, R., E. Jin, H. Levinson, A. Isles, and P. C. Fleming. 1983. Ceftazidime alone and in combination in patients with cystic fibrosis: lack of efficacy in treatment of severe respiratory infections caused by Pseudomonas cepacia. J. Antimicrob. Chemother. 12(Suppl. A):331-336. |
| 16. |
Govan, J. R. W.,
J. E. Hugues, and P. Vandamme.
1996.
Burkholderia cepacia: medical, taxonomic and ecological issues.
J. Med. Microbiol.
45:395-407 |
| 17. | Govan, J. R. W., P. H. Brown, J. Maddison, C. J. Doherty, J. W. Nelson, M. Dodd, A. P. Greening, and A. K. Webb. 1993. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 342:15-19[Medline]. |
| 18. | Hoiby, N., O. Ciofu, T. Jensen, T. Pressler, H. K. Johansen, and C. Koch. 1996. Use of carbapenems and other antibiotics for pulmonary infections in patients with cystic fibrosis. Pediatr. Infect. Dis. J. 15:738-743[Medline]. |
| 19. |
Hoogkamp-Korstanje, J. A. A., and J. van der Laag.
1983.
Piperacillin and tobramycin in the treatment of Pseudomonas lung infections in cystic fibrosis.
J. Antimicrob. Chemother.
12:175-183 |
| 20. | Hutchinson, M., K. L. Faulkner, P. J. Turner, S. J. Haworth, W. Sheik, H. Nadler, and D. H. Pitkin. 1995. A compilation of meropenem tissue distribution data. J. Antimicrob. Chemother. 36(Suppl. A):43-56. |
| 21. |
Jacoby, G. A., and L. Sutton.
1989.
Pseudomonas cepacia susceptibility to sulbactam.
Antimicrob. Agents Chemother.
33:583-584 |
| 22. | Johnson, C. C. 1996. In vitro testing: correlations between bacterial susceptibility, body fluids levels, and effectiveness of antibacterial therapy, p. 813-834. In V. Lorian (ed.), Antibiotics in laboratory medicine, 4th ed. The Williams & Wilkins Co., Baltimore, Md. |
| 23. | Kucers, A., and N. M. Bennett. 1987. Rifampicin, p. 914-970. In N. M. Bennett (ed.), The use of antibiotics, 4th ed. Heinemann Medical Books, Oxford, United Kingdom. |
| 24. |
Kumar, A.,
R. Wofford-McQueen, and R. C. Gordon.
1989.
Ciprofloxacin, imipenem and rifampicin: in-vitro synergy of two and three drug combinations against Pseudomonas cepacia.
J. Antimicrob. Chemother.
23:831-835 |
| 25. | Legge, J. S., T. M. Reid, and J. B. Palmer. 1985. Clinical efficacy, tolerance and pharmacokinetics of temocillin in patients with respiratory tract infections. Drugs 29(Suppl. 5):118-121. |
| 26. |
Lewin, C.,
C. Doherty, and J. Govan.
1993.
In vitro activities of meropenem, PD 127391, PD 131628, ceftazidime, chloramphenicol, co-trimoxazole, and ciprofloxacin against Pseudomonas cepacia.
Antimicrob. Agents Chemother.
37:123-125 |
| 27. | Lu, D. C. T., S. C. Chang, Y. C. Chen, K. T. Luh, and W. C. Hsieh. 1997. In vitro activities of antimicrobial agents, alone and in combinations against Burkholderia cepacia isolated from blood. Diagn. Microbiol. Infect. Dis. 28:187-191[Medline]. |
| 28. |
Moore, R. A., and R. E. W. Hancock.
1986.
Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance.
Antimicrob. Agents Chemother.
30:923-926 |
| 29. | National Committee for Clinical Laboratory Standards. 1993. Performance for antimicrobial disk susceptibility tests, 5th ed. Approved standard M2-A5. National Committee for Clinical Laboratory Standards, Wayne, Pa. |
| 30. | National Committee for Clinical Laboratory Standards. 1997. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. Approved standard M7 A4. National Committee for Clinical Laboratory Standards, Wayne, Pa. |
| 31. | National Committee for Clinical Laboratory Standards. 1998. Performance for antimicrobial susceptibility testing. Eighth informational supplement. M100 S8. National Committee for Clinical Laboratory Standards, Wayne, Pa. |
| 32. |
Parr, T. R., Jr.,
R. A. Moore,
L. V. Moore, and R. E. W. Hancock.
1987.
Role of porins in intrinsic antibiotic resistance of Pseudomonas cepacia.
Antimicrob. Agents Chemother.
31:121-123 |
| 33. |
Pitt, T. L.,
M. E. Kaufmann,
P. S. Patel,
L. C. A. Benge,
S. Gaskin, and D. M. Livermore.
1996.
Type characterisation and antibiotic susceptibility of Burkholderia (Pseudomonas) cepacia isolates from patients with cystic fibrosis in the United Kingdom and the Republic of Ireland.
J. Med. Microbiol.
44:203-210 |
| 34. |
Prince, A.,
M. S. Wood,
G. S. Cacalano, and N. X. Chin.
1988.
Isolation and characterization of a penicillinase from Pseudomonas cepacia 249.
Antimicrob. Agents Chemother.
32:838-843 |
| 35. |
Scordilis, G. E.,
H. Ree, and T. G. Lessie.
1987.
Identification of transposable elements which activate gene expression in Pseudomonas cepacia.
J. Bacteriol.
169:8-13 |
| 36. | Segonds, C., E. Bingen, G. Couetdic, S. Mathy, N. Brahimi, N. Marty, P. Plesiat, Y. Michel-Briand, and G. Chabanon. 1997. Genotypic analysis of Burkholderia cepacia isolates from 13 French cystic fibrosis centers. J. Clin. Microbiol. 35:2055-2060[Abstract]. |
| 37. |
Smith, M. J.,
L. O. White,
H. Bowyer,
J. Willis,
M. E. Hodson, and J. C. Batten.
1986.
Pharmacokinetics and sputum penetration of ciprofloxacin in patients with cystic fibrosis.
Antimicrob. Agents Chemother.
30:614-616 |
| 38. |
Strandvik, B.,
A. S. Malmborg,
T. Bergan,
H. Michalsen,
O. T. Storrosten, and B. Wretlind.
1988.
Imipenem/cilastatin, an alternative treatment of Pseudomonas infection in cystic fibrosis.
J. Antimicrob. Chemother.
21:471-480 |
| 39. | Tablan, O. C., T. L. Chorba, D. V. Schidlow, J. W. White, K. A. Hardy, P. H. Gilligan, W. M. Morgan, L. A. Carson, W. J. Martone, J. M. Jason, and W. R. Jarvis. 1985. Pseudomonas cepacia colonization in patients with cystic fibrosis: risks factors and clinical outcome. J. Pediatr. 107:382-387[Medline]. |
| 40. |
Taylor, R. F. H.,
H. Gaya, and M. E. Hodson.
1992.
Temocillin and cystic fibrosis. outcome of intravenous administration in patients infected with Pseudomonas cepacia.
J. Antimicrob. Chemother.
29:341-344 |
| 41. |
Turner, A.,
S. J. Pedler,
F. Carswell,
G. R. Spencer, and D. C. E. Speller.
1984.
Serum and sputum concentrations of ceftazidime in patients with cystic fibrosis.
J. Antimicrob. Chemother.
14:521-527 |
| 42. |
Vandamme, P.,
B. Holmes,
M. Vancanneyt,
T. Coenye,
B. Hoste,
R. Coopman,
H. Revets,
S. Lauwers,
M. Gillis,
K. Kersters, and J. R. W. Gowan.
1997.
Occurrence of multiple genomovars of Burkholderia cepacia in cystic fibrosis patients and proposal of Burkholderia multivorans sp. nov.
Int. J. Syst. Bacteriol.
47:1188-1200 |
| 43. |
Visalli, M., A.,
M. R. Jacobs, and P. C. Appelbaum.
1998.
Activities of three quinolones alone and in combination with extended-spectrum cephalosporins or gentamicin against Stenotrophomonas maltophilia.
Antimicrob. Agents Chemother.
42:2002-2005 |
| 44. | Visalli, M., A., S. Bajaksouzian, M. R. Jacobs, and P. C. Appelbaum. 1997. Comparative activity of trovafloxacin, alone and in combination with other agents, against gram-negative nonfermentative rods. Antimicrob. Agents Chemother. 41:1475-1481[Abstract]. |
| 45. |
Yourassovsky, E.,
M. P. Van der Linden,
F. Crokaert, and Y. Glupczynski.
1988.
Effect of antibiotics carry-over on bacterial counting by "spiral plating."
J. Antimicrob. Chemother.
21:138-140 |
| 46. |
Yu, V. L.,
J. J. Zuravleff,
J. E. Peacock,
D. Dehertogh, and L. Tashjian.
1984.
Addition of rifampin to carboxypenicillin-aminoglycoside combination for the treatment of Pseudomonas aeruginosa infection: clinical experience with four patients.
Antimicrob. Agents Chemother.
26:575-577 |
| 47. | Zuravleff, J. J., V. L. Yu, and R. B. Yee. 1983. Ticarcillin-tobramycin-rifampin: in vitro synergy of the triplet combination against Pseudomonas aeruginosa. J. Lab. Clin. Med. 101:896-902[Medline]. |
Antimicrobial Agents and Chemotherapy, February 1999, p. 213-217, Vol. 43, No. 2
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