Antibiotic therapy for Pseudomonas aeruginosa bacteremia: Outcome correlations in a prospective study of 200 patients

doi:10.1016/S0002-9343(89)80611-4

The American Journal of Medicine

Volume 87, Issue 5, November 1989, Pages 540-546

https://doi.org/10.1016/S0002-9343(89)80611-4 Get rights and content

Purpose and patients and methods

We performed a prospective clinical study of 200 consecutive patients with Pseudomonas aeruginosa bacteremias to analyze in vitro susceptibility and synergistic testing of antibiotics the patients received and clinical parameters to assess their relationship to survival.

Results

No significant correlation between in vitro susceptibility testing (minimal inhibitory concentrations/minimal bactericidal concentrations) and outcome could be demonstrated. Similarly, improved outcome could not be demonstrated for patients receiving antibiotic combinations that were synergistic in vitro (either time-kill or checkerboard) versus those combinations that were not. There was also no correlation between results obtained by time-kill curve and checkerboard synergistic testing, i.e., combinations found to be synergistic by one method were not necessarily synergistic by the other method. Clinical parameters associated with improved survival were a urinary portal of entry and absence of neutropenia. Conversely, survival was significantly decreased when the portal was the respiratory tract The mortality rate between patients receiving combination therapy (27%) and monotherapy (47%) was significant (p <0.02); this significant relationship held true for most subgroups including malignancy, nosocomial infection, and infection site.

Conclusion

Increasing effort should be placed on ensuring timely administration of combination therapy to patients with P. aeruginosa bacteremia since the use of combination therapy was even more important in determining outcome than was underlying disease.

References (62)

FlickMR et al.
Pseudomonas bacteremia: review of 108 cases
Am J Med
(1976)
ElionGB et al.
Antagonist of nucleic acid derivatives. VIII. Synergism in combination of biochemically related metabolites
J Biol Chem
(1954)
LauWK et al.
Comparative efficacy and toxicity of amikacin/carbenicillin versus gentamicin/carbenicillin in leukopenic patients—a randomized prospective trial
Am J Med
(1977)
BaltchAL et al.
Combinations of antibiotics against Pseudomonas aeruginosa
Am J Med
(1985)
BennettJV
Hospital acquired infections and the altered hosts: nosocomial infections due to Pseudomonas
J Infect Dis
(1974)
CrossA et al.
Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends
Rev Infect Dis
(1983)
FishmanLS et al.
Pseudomonas aeruginosa bacteremia in patients with neoplastic disease
Cancer
(1972)
AllenJR et al.
Secular trends in nosocomial infections: 1970–1979
Am J Med
(1981)
BaltchAL et al.
Pseudomonas aeruginosa bacteremia: susceptibility of 100 blood culture isolates to seven antimicrobial agents and its clinical significance
J Lab Clin Med
(1979)
TapperML et al.
Bacteremia due to Pseudomonas aeruginosa complicating neoplastic disease: a progress report
J Infect Dis
(1974)

WhitecarJP et al.

Pseudomonas bacteremia in patients with malignant disease

Am J Med Sci

(1970)

FassRJ et al.

Interaction of clindamycin and gentamicin in vitro

Antimicrob Agent Chemother

(1974)

BulgerRJ et al.

Effect of different media on in vitro studies of antibiotic combination

Appl Microbiol

(1968)

KaplanEL et al.

Nonparametric estimation from incomplete observations

J Am Stat Assoc

(1958)

MantelN

Evaluation of survival data and two new rank order statistics arising in its consideration

Cancer Chemother Rep

(1966)

BreslowN

A generalized Kruskal-Wallis test for comparing K samples subject to unequal patterns of censorship

Biometrika

(1970)

EllnerPD et al.

The inhibitory quotient: a method for interpreting minimum inhibitory concentration data

JAMA

(1981)

BerenbaumMC

Correlations between methods for measurement of synergy

J Infect Dis

(1980)

ComberKR et al.

Synergy of carbenicillin and gentamicin in experimental infections with Pseudomonas

J Infect Dis

(1971)

GiamarellouH

Aminoglycoside plus beta-lactam against gram-negative organisms—evaluation of in vitro synergy and chemical interactions

Am J Med

(1986)

ChandrasekarPH et al.

Comparison of the activity of antibiotic combinations in vitro with clinical outcome and resistance emergence in serious infections by Pseudomonas aeruginosa in nonneutropenic patients

J Antimicrob Chemotner

(1987)

BodeyGP et al.

Pseudomonas bacteremia; retrospective analysis of 410 episodes

Arch Intern Med

(1985)

YoungLS

Empirical antimicrobial therapy in the neutropenic host

N Engl J Med

(1986)

MoelleringRC

Antimicrobial synergism—an elusive concept

J Infect Dis

(1979)

MarymontJH et al.

Laboratory evaluation of antibiotic combinations: a review of methods and problems

Lab Med

(1981)

KrogstadDJ et al.

Antibiotics in laboratory medicine

WeinsteinRJ et al.

Comparison of methods for assessing in vitro antibiotic synergism against Pseudomonas and Serratia

J Lab Clin Med

(1975)

NordenCW et al.

Comparison of techniques for measurement of in vitro antibiotic synergism

J Infect Dis

(1979)

WoolfreyBF et al.

Broth microdilution testing of Pseudomonas aeruginosa and aminoglycosides: need for employing dilutions differing by small arithmetic increments

J Clin Microbiol

(1982)

HallanderHO et al.

Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method

Antimicrob Agents Chemother

(1982)

YoungLS

Significance of in vitro tests

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Clinical studyAntibiotic therapy for Pseudomonas aeruginosa bacteremia: Outcome correlations in a prospective study of 200 patients*

Purpose and patients and methods

Results

Conclusion

Am J Med

J Biol Chem

Am J Med

Combinations of antibiotics against Pseudomonas aeruginosa

Am J Med

Hospital acquired infections and the altered hosts: nosocomial infections due to Pseudomonas

J Infect Dis

Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends

Rev Infect Dis

Pseudomonas aeruginosa bacteremia in patients with neoplastic disease

Cancer

Secular trends in nosocomial infections: 1970–1979

Am J Med

Pseudomonas aeruginosa bacteremia: susceptibility of 100 blood culture isolates to seven antimicrobial agents and its clinical significance

J Lab Clin Med

Bacteremia due to Pseudomonas aeruginosa complicating neoplastic disease: a progress report

J Infect Dis

Pseudomonas bacteremia in patients with malignant disease

Am J Med Sci

Interaction of clindamycin and gentamicin in vitro

Antimicrob Agent Chemother

Effect of different media on in vitro studies of antibiotic combination

Appl Microbiol

Nonparametric estimation from incomplete observations

J Am Stat Assoc

Evaluation of survival data and two new rank order statistics arising in its consideration

Cancer Chemother Rep

A generalized Kruskal-Wallis test for comparing K samples subject to unequal patterns of censorship

Biometrika

The inhibitory quotient: a method for interpreting minimum inhibitory concentration data

JAMA

Correlations between methods for measurement of synergy

J Infect Dis

Synergy of carbenicillin and gentamicin in experimental infections with Pseudomonas

J Infect Dis

Aminoglycoside plus beta-lactam against gram-negative organisms—evaluation of in vitro synergy and chemical interactions

Am J Med

Comparison of the activity of antibiotic combinations in vitro with clinical outcome and resistance emergence in serious infections by Pseudomonas aeruginosa in nonneutropenic patients

J Antimicrob Chemotner

Pseudomonas bacteremia; retrospective analysis of 410 episodes

Arch Intern Med

Empirical antimicrobial therapy in the neutropenic host

N Engl J Med

Antimicrobial synergism—an elusive concept

J Infect Dis

Laboratory evaluation of antibiotic combinations: a review of methods and problems

Lab Med

Antibiotics in laboratory medicine

Comparison of methods for assessing in vitro antibiotic synergism against Pseudomonas and Serratia

J Lab Clin Med

Comparison of techniques for measurement of in vitro antibiotic synergism

J Infect Dis

Broth microdilution testing of Pseudomonas aeruginosa and aminoglycosides: need for employing dilutions differing by small arithmetic increments

J Clin Microbiol

Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method

Antimicrob Agents Chemother

Significance of in vitro tests

Clinical study
Antibiotic therapy for Pseudomonas aeruginosa bacteremia: Outcome correlations in a prospective study of 200 patients*