Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia

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      To determine the association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia, the case reports of 37 patients from four prospective, randomized, controlled trials of gentamicin, tobramycin, and amikacin were analyzed. Twenty (54 percent) of these patients had a favorable outcome. Patients with maximal one-hour postinfusion (peak) levels of 7 μg/ml or greater for gentamicin and tobramycin or 28 μg/ml or greater for amikacin more often had successful outcomes (14 of 18, 78 percent) than those with levels less than this (six of 19, 32 percent) (p < 0.006). Patients with overall mean peak levels of 6 μg/ml or greater for gentamicin and tobramycin or 24 μg/ml or greater for amikacin more often had successful outcomes (14 of 20, 70 percent) than those with levels less than this (six of 17, 35 percent) (p < 0.04). The initial patient temperature, serum urea nitrogen/creatinine ratio, initial polymorphonuclear leukocyte count, and age were also associated with outcome; but by multivariate analysis, achieving an adequate peak concentration was the most important discriminating factor. These results suggest the potential importance of achieving adequate aminoglycoside levels in patients with gram-negative pneumonia.
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        • McHenry MC
        • Alfidi RJ
        • Devillar SO
        • Braun WE
        • Popowniak KL
        Hospital-acquired pneumonia.
        Med Clin North Am. 1974; 58: 565-580
        • Briggs DD
        Pulmonary infections.
        Med Clin North Am. 1977; 66: 1163-1183
        • LaForce FM
        Hospital-acquired gram-negative rod pneumonias: an overview.
        Am J Med. 1981; 70: 664-669
        • Trenholme GM
        • McKellar PP
        • Rivera N
        • Levin S
        Amikacin in the treatment of gram-negataive pneumonia.
        Am J Med. 1977; 62: 949-953
        • Van der Straeten M
        • Paurels R
        • Pijek J
        • Nimmen LV
        • Klumphens P
        • Soep H
        Amikacin in the treatment of gram-negative bronchopulmonary infections.
        J Infect Dis. 1976; 134 (suppl): 391-393
        • Gross PA
        • New HC
        • Ascopokea P
        • Van Antwerpin C
        • Aswapakee N
        Deaths from nosocomial infections: experience in a university hospital and a community hospital.
        Am J Med. 1980; 68: 219-223
        • Neu HC
        Clinical use of aminoglycosides.
        in: Whelton A Neu HC The aminoglycosides. Microbiology, clinical use and toxicology. Marcel Dekker, New York1982: 611-628
        • Noone P
        • Pattison JR
        • Garfield Danies D
        The effective use of gentamicin in life-threatening sepsis.
        Postgrad Med J. 1974; 50: 9-16
        • Smith CR
        • Baughman KL
        • Edwards CQ
        • Rogers FJ
        • Lietman PS
        Controlled comparison of amikacin and gentamicin.
        N Engl J Med. 1977; 296: 349-353
        • Wade JC
        • Smith CR
        • Petty BG
        • et al.
        Cephalothin plus an aminoglycoside is more nephrotoxic than methicillin plus an aminoglycoside.
        Lancet. 1978; II: 604-606
        • Smith CR
        • Lipsky JJ
        • Laskin OL
        • Hellman DB
        • Longstreth J
        • Lietman PS
        Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin.
        N Engl J Med. 1980; 302: 1106-1109
      1. Smith CR, Ambinder RF, Lipsky JJ, et al: Cefotaxime vs. nafcillin-tobramycin for serious bacterial infection: a randomized double-blind trial. Ann Intern Med (in press).

        • Chan RA
        • Brenner EJ
        • Hoeprich PD
        Gentamicin therapy in renal failure: a nomogram for dosage.
        Ann Intern Med. 1972; 76: 773-778
        • Smith DH
        • VanOtto B
        • Smith AL
        A rapid chemical assay for gentamicin.
        N Engl J Med. 1972; 286: 583-586
        • McCabe WR
        • Jackson GG
        Gram-negative bacteremia II. Clinical, laboratory and therapeutic observations.
        Arch Intern Med. 1962; 110: 856-864
        • Nie NH
        • Hull CH
        • Jenkins JG
        • Steinbrenner K
        • Bent DH
        Statistical package for the social sciences.
        2nd ed. McGraw-Hill, New York1975
      2. Ray Aa Statistical analysis system. SAS Institute, Inc, Cary, North Carolina1982
        • Johanson WG
        Significance of colonization of the respiratory tract by gram-negative bacilli.
        in: Thys JP Klastersky J Yourossousky E Aerobic gram-negative bronchopneumonias. Pergamon, Oxford, England1980: 17-27
        • Louria DB
        • Young L
        • Armstrong D
        • Smith JK
        Gentamicin in the treatment of pulmonary infections.
        J Infect Dis. 1969; 119: 483-485
        • Bendush CL
        • Weber R
        Tobramycin sulfate: a summary of worldwide experience from clinical trials.
        J Infect Dis. 1976; 134 (suppl): 219-234
        • Lewis RP
        • Meyer RD
        • Finegold SM
        Amikacin therapy of patients with gentamicin-resistant gram-negative bacillary infection.
        Am J Med. 1977; 62 (suppl): 142-150
        • Craven PC
        • Jorgensen JH
        • Kasper RL
        • Drutz DJ
        Amikacin therapy of patients with multiple antibiotic resistant Serratia marcessens infections.
        Am J Med. 1977; 62 (suppl): 66
        • Altucci P
        • Albate GF
        • Gattoni A
        • Leonossa V
        Clinical evaluation of tobramycin in respiratory and system infections in immunosuppressed and normal patients.
        J Infect Dis. 1976; 134 (suppl): 139-141
        • Flick MR
        • Cluff LE
        Pseudomonas bacteremia. review of 108 cases.
        Am J Med. 1976; 60: 501-508
        • Parry MF
        • New HC
        A comparative study of ticarcillin plus tobramycin versus carbenicillin plus gentamicin for the treatment of serious infections due to gram-negative bacilli.
        Am J Med. 1978; 64: 961-966
        • Wang GA
        • Peirce TH
        • Goldstein E
        • Haeprich PP
        Penetration of antimicrobial agents into bronchial secretions.
        Am J Med. 1975; 59: 219-223
        • Alexander MR
        • Berglund BC
        • Kasik JE
        • Fox A
        • Chinn WM
        The concentration of tobramycin in bronchial secretions.
        Chest. 1979; 75: 675-678
        • Dull WL
        • Alexander MR
        • Kasik JE
        Bronchial secretion levels of amikacin.
        Antimicrob Agents Chemother. 1979; 16: 767-771
        • Hull WH
        • Derding DN
        • Schiel EA
        Penetration of tobramycin into infected extravascular fluids and its therapeutic effectiveness.
        J Infect Dis. 1977; 135: 957-961
        • Moore RD
        • Smith CR
        • Lietman PS
        The association of aminoglycoside plasma levels with mortality in gram-negative bacteremia.
        J Infect Dis. 1984; 149: 443-448
        • Barza M
        • Brown RB
        • Shen D
        • Gilaldi M
        • Weinstein L
        Predictability of blood levels of gentamicin in man.
        J Infect Dis. 1975; 132: 165-174
        • Kaye D
        • Levison ME
        • Laboritz ED
        The unpredictability of serum concentrations of gentamicin: pharmacokinetics of gentamicin in patients with normal renal function.
        J Infect Dis. 1974; 130: 150-154