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Susceptibility of 100 blood isolates of Pseudomonas aeruginosa to 19 antipseudomonal antibiotics: Old and new
DIAGNMICROBIALINFECT DIS 1987;7:107-111
107
ANTIMICROBIAL SUSCEPTIBILITY STUDIES
Susceptibility of 100 Blood Isolates of Pseudomonas aeruginosa to 19 Antipseudomonal Antibiotics: Old and New Joyce Korvick, Victor L. Yu, and Megan Hilf
The in vitro susceptibility of 19 antipseudomanal antibiotics, old and new, were tested against 100 blood isolates of Pseudomonas aeruginosa. The isolates were taken from consecutive bacteremic patients hospitalized in nine Pittsburgh hospitals from 1983 to 1984. Twelve percent of isolates tested were tobramycin-resistant. All of the tabramycin-resistont isolates were sensitive to apalcillin, azlocillin, aztreonam, cefsulodin, ceftazidime, ciprofloxicin, and imipenem. Two isolates were resistant in vitro to all 13-1actam antibiotics tested, but sensitive to all aminoglycasides. One hundred percent of isolates tested were susceptible to imipenem, whereas, 98% were susceptible to apalcillin and cefsulodin. The lowest MICgo was 2 mg/L for ciprofloxicin. Tolerance of P. aeruginosa (MICgo/MBC9oratio > 32J was nat observed for any antimicrobial agent.
INTRODUCTION Despite the continuing i n t r o d u c t i o n of potent a n t i p s e u d o m o n a l antibiotics, Pseudomonas aeruginosa r e m a i n s a serious pathogen. The mortality rate of p s e u d o m o n a l bacteremia can exceed 70% and it a p p r o a c h e s 90% w h e n the portal of entry is the respiratory tract (Baltch a n d Griffin, 1977; Flick and Cluff, 1976; T a p p e r and Armstrong, 1974). One reason for this high mortality is its notable resistance to m a n y currently available antibiotics (Yu et el., 1980; Van der A u w e r a and Schuyteneer, 1983). Given the increasing n u m b e r s of a n t i p s e u d o m o n a l agents, we sought to p r o v i d e a clinically relevant comparison, i.e., s i m u l t a n e o u s susceptibility testing w i t h a large number of significant clinical isolates and a large n u m b e r of antibiotics, both old and new. This a p p r o a c h avoids the p r o b l e m s of differences in laboratory m e t h o d ology, institution-associated resistance patterns, and other variables that arise w h e n agents are c o m p a r e d on the basis of p u b l i s h e d susceptibility data from different laboratories. Therefore, w e tested 100 consecutive P. aeruginosa isolated from the blood in patients from nine Pittsburgh hospitals against 19 a n t i p s e u d o m o n a l antibiotics.
From the VA Medical Center and University of Pittsburgh, Pittsburgh, PA. Address reprint requests to: Victor L. Yu, M.D., University of Pittsburgh School of Medicine, Scaife 968, Pittsburgh, PA 15261. Received September 24, 1986; revised and accepted January 29, 1987.
© 1987 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Avenue, New York, NY 10017
0732-8893/87/$03.50
108
J. Korvick et al.
MATERIALS AND METHODS Organisms One hundred consecutive P. aeruginosa blood isolates were obtained from patients hospitalized from 1983 to 1984 at the following Pittsburgh hospitals: VA Medical Center, Presbyterian University Hospital, Allegheny General Hospital, Mercy Hospital, Montefiore Hospital, Shadyside Hospital, St. Francis Hospital, Washington Hospital, and West Penn Hospital. ATCC 27853 was used as a control strain.
Antibiotics Reagent grade powders were supplied by the manufacturers. Each antibiotic powder was dissolved in sterile solutions as specified by the manufacturer to obtain a stock solution. Serial dilutions were then made with Mueller-Hinton broth (Difco, Detroit, MI), which was supplemented with 60 mg/L calcium and 20 mg/L magnesium.
In Vitro Susceptibility Testing An inoculum of each organism was prepared in trypticase soy broth and incubated for 4-6 hr to achieve log-growth-phase. Each sample was matched to a 0.5 MacFarland standard and diluted 1:200. Fifty microliters were placed in each well of two columns of a microtiter plate. The final concentration of the inoculum was approximately 5 x 10 s CFU/ml. Viable counts of the inoculum were performed using a spiral plate system (Spiral Systems Inc., Bethesda, MD). This device dispenses 40 ~L of inoculum on agar plates in spiral formation by logarithmic increments in volume. The plates were incubated 20 hr and counted. Minimum inhibitory concentrations (MIC) were determined with microtiter dilution techniques (Jones et al., 1985). Fifty microliters of supplemented Mueller-Hinton broth were added to each well of a sterile, 96-well microtiter plate (Flow Laboratories, McLean, VA). Fifty microliters of the working antibiotic solution were added to the first row of each column and serial twofold dilutions were then made with a sterile microdiluter (Titertek, Flow Labs, McLean, VA). These plates were placed in a humidified incubator for 20 hr at 37°C. The MIC endpoints were defined as the lowest antibiotic concentration providing a clear well for visual inspection. Minimum bactericidal concentrations (MBC) were performed in concert with the MICs. Ten microliter aliquots were removed from each of the last three wells of a column showing no growth and placed onto agar based medium. These plates were incubated at 37°C for 20 hr before reading. MBCs were defined as the concentration of the antibiotic which provided 99.9% kill. Each set of MIC/MBCs were performed in duplicate on different days.
RESULTS Table 2 shows the cumulative susceptibilities for each antibiotic. One hundred percent of isolates were susceptible to imipenem, whereas, 98% were susceptible to apalcillin, and 97% were susceptible to cefsulodin and cefpiramide. Although the MIC9o for tobramycin was >256 mg/L, the distribution was bimodal; 88% of the isolates were sensitive to tobramycin at MICs of 4 mg/L or less. Of the 100 P. areuginosa blood isolates, 12% were tobramycin-resistant. All of the tobramycin-resistant isolates were susceptible to apalcillin, azlociUin, aztreonam, cefsulodin, ceftazidime, ciprofloxicin, and imipenem. Two isolates were resistant in
Antibiotic Susceptibilities of P. Aeruginosa
109
TABLE 1. MICs and MBCs of 100 P s e u d o m o n a s aeruginosa Blood Isolates Using 19 A n t i p s e u d o m o n a l Agents, Old a n d New Antibiotic
MICso
MICgo
Ceftazidime Cefsulodin Cefpiramide° Cefoperazone Cefpirome (HR810)a Cefpimazole a
4 4 4 8 16 16
Apalcillin° Piperacillin Azlocillin Ticarcillin Mezlocillin Carbenicillin
2 8 8 32 64 64
8 16 32 128 128 128
Tobramycin Amikacin Gentamicin Netilmicin
2 8 4 16
>256 16 32 32
0.5 1 8
2 4 16
Range
MBCso
MBCgo
Range
4 8 8 16 32 32
16 128 32 128 64 128
1->256 1-128 1->128 4->512 4-256 2-<512
8 8 16 32 64 128
32 64 128 128 256 512
1-512 1->512 4->512 8->1024 32->1024 8->512
2 16 8 32
256 32 >256 64
0.5->512 1->64 2->1024 <0.06->256
1 2 8
2 8 32
Cephalosporins 16 16 16 32 32 64
0.5-128 1-128 1->512 1->512 4-256 2->512
Antipseudomonal Penicillins 0.5-512 1->512 2->512 0.5->1024 8->1024 8->512
Aminoglycosides 0.13-512 1-64 1->1024 <0.06->256
Others Ciprofloxacin ° Imipenem Aztreonama
<0.06-4 0.5-8 0.5-128
<0.06->8 0.5->16 1-128
aInvestigational.
vitro to all B-lactam antibiotics but sensitive to all aminoglycosides. Results of MIC/ MBC testing are s h o w n in Table 1. Tolerance, as defined by a MBCgo/MICgo ratio of >32 was not seen for any agent (Thrupp, 1986). DISCUSSION We sought to compare newer a n t i p s e u d o m o n a l agents with older established agents using recent (1983-1984) clinical blood isolates. The isolates were taken from n i n e Pittsburgh hospitals i n c l u d i n g a university referral hospital, a county general hospital, a VA hospital, and c o m m u n i t y hospitals; these hospitals provide a diverse source of organisms. We caution that the use of the MIC and/or MBC alone is inadequate for evaluating antibiotic potency. The inhibitory quotient (Ellner and Neu, 1981), a ratio of peak serum concentration of antibiotic to MIC, has also been used for antibiotic comparison. Using this ratio, i m i p e n e m , aztreonam, and cefpiramide appear to have the highest values. However, this ratio fails to take into account other factors, e.g., degree of protein binding, pH, penetration of antibiotic into target tissue, the area u n d e r the serum concentration time curve measuring total time of exposure of the organism to a given agent ("area u n d e r the curve"}. Nevertheless, this comprehensive study per-
110
J. K o r v i c k et al.
TABLE 2. C u m m u l a t i v e S u s c e p t i b i l i t i e s of 100 P s e u d o m o n a l B l o o d I s o l a t e s to 19 Antipseudomonal Antibiotics Cumulative percentage of isolates inhibited at dose (mg/L) Antibiotic
~0.5
1
2
8 3 2 1
42 28 15 2
4
8
16
32
64
128
9256
Susceptible (°/o)a
99 99 99 94 99 91
100 100 100 98
100 100 100
88 97 97 85 94 67
93 96 93 92
100 100 100 100 100 100
98 90 92 44 6 92
89
100
88 95 56 5
Cephalosporins Ceftazidime Cefsulodin Cefpiramide Cefoperazone Cefpirome Cefpimazole
1
Apalcillin PiperaciUin Azlocillin Ticarcillin Mezlocillin Carbenicillin
1
Tobramycin Amikacin Gentamicin Netilmicin
18
Ciprofloxacin Imipenem Az~eonam
56 12 1
7
71 73 55 18 7 16
88 88 85 66 33 35
94 97 94 85 79 67
97 98 97 93 94 89
96
Antipseudomonal Penicillins 13 1
59 2
87 43 14
1
94 79 57 2 1 1
98 90 85 44 6
99 93 92
97
77
89 79 57
32 10
Aminoglycosides 49 1 2
78 4 17 3
88 32 56 5
87 54
97 88 7
100 98 49
1
68 84 26
95 89 72
100 90 93
91 99
100 100
Others 100 74
91
96
99
100
87 100 74
°Isolates were considered susceptible if MIC was: ~1 for ciprofloxacin; ~4 for gentamicin, tobramycin, netilmicin; ~<8 for aztreonam, ceftazidime, imipenem; ~<16 for cefsulodim, cefoperazone, cefpimazole, piperacillin, ticarcillin, mezlocillin, apalcillin, amikacin; ~<32 for cefpiramide, cefpirome; ~64 for azlocillin; ~<128 for carbenicillin.
f o r m e d in o n e l a b o r a t o r y for 100 c o n s e c u t i v e b l o o d i s o l a t e s p r o v i d e s d a t a t h a t c a n be u s e d d i r e c t l y or i n c a l c u l a t i o n s for f u r t h e r c o m p a r i s o n s . In c o n c l u s i o n , w e s h o w t h a t t h e s e n e w e r a g e n t s are q u i t e p o t e n t i n v i t r o a g a i n s t P. aeruginosa a n d w o u l d a p p e a r to h a v e c o n s i d e r a b l e p o t e n t i a l i n t h e c l i n i c a l arena. F u r t h e r trials i n ill s u b j e c t s w i l l u l t i m a t e l y d e t e r m i n e t h e efficacy of e a c h agent.
REFERENCES Baltch AL, Griffin P (1977) Fseudomonas aeruginosa bacteremia: A clinical study of 75 patients. Am J Med Sci 274:119. Ellner P, Neu H (1981) The inhibitory quotient, a method for interpreting minimum inhibitory concentration data. J Am Med Assoc 246:1575. Flick MR, Cluff LE (1976) Pseudomonas bacteremia, a review of 180 cases. Am J Mad 60:501. Jones RN, Barry AL, Gavan TL, Washington JA (1985) Susceptibility tests: Microdilution and macrodilution broth procedures. In: Manual of Clinical Microbiology, 4th ed. Eds., Lennette EH, Balows A, Hausler WJ, Shadomy HJ. Washington, DC: American Society for Microbiology, pp. 972-977. Tapper M, Armstrong D (19741 Bacteremia due to Pseudomonas aeruginosa complicating neoplastic disease: A progress report. J Infect Dis 130(suppl):514.
Antibiotic Susceptibilities of P. Aeruginosa
111
Thrupp L (1986) Susceptibility testing of antibiotics in liquid media. In: Antibiotics in Laboratory Medicine, 2nd ed. Ed., Lorian V. Baltimore, MD: Williams & Wilkins, pp. 93-150. Van der Auwera P, Schuyteneer F (1983) In vitro susceptibility of Pseudomonas aeruginosa to old and new beta lactam antibiotics and aminoglycosides. J Antimicrob Chemother 11:511. Yu VL, Vickers RM, Zuravleff J] (1980) Comparative susceptibilities to moxalactam and eight other antipseudomonal antimicrobial agents (old and new). Antimicrob Agents Chemother 17:96.
107
ANTIMICROBIAL SUSCEPTIBILITY STUDIES
Susceptibility of 100 Blood Isolates of Pseudomonas aeruginosa to 19 Antipseudomonal Antibiotics: Old and New Joyce Korvick, Victor L. Yu, and Megan Hilf
The in vitro susceptibility of 19 antipseudomanal antibiotics, old and new, were tested against 100 blood isolates of Pseudomonas aeruginosa. The isolates were taken from consecutive bacteremic patients hospitalized in nine Pittsburgh hospitals from 1983 to 1984. Twelve percent of isolates tested were tobramycin-resistant. All of the tabramycin-resistont isolates were sensitive to apalcillin, azlocillin, aztreonam, cefsulodin, ceftazidime, ciprofloxicin, and imipenem. Two isolates were resistant in vitro to all 13-1actam antibiotics tested, but sensitive to all aminoglycasides. One hundred percent of isolates tested were susceptible to imipenem, whereas, 98% were susceptible to apalcillin and cefsulodin. The lowest MICgo was 2 mg/L for ciprofloxicin. Tolerance of P. aeruginosa (MICgo/MBC9oratio > 32J was nat observed for any antimicrobial agent.
INTRODUCTION Despite the continuing i n t r o d u c t i o n of potent a n t i p s e u d o m o n a l antibiotics, Pseudomonas aeruginosa r e m a i n s a serious pathogen. The mortality rate of p s e u d o m o n a l bacteremia can exceed 70% and it a p p r o a c h e s 90% w h e n the portal of entry is the respiratory tract (Baltch a n d Griffin, 1977; Flick and Cluff, 1976; T a p p e r and Armstrong, 1974). One reason for this high mortality is its notable resistance to m a n y currently available antibiotics (Yu et el., 1980; Van der A u w e r a and Schuyteneer, 1983). Given the increasing n u m b e r s of a n t i p s e u d o m o n a l agents, we sought to p r o v i d e a clinically relevant comparison, i.e., s i m u l t a n e o u s susceptibility testing w i t h a large number of significant clinical isolates and a large n u m b e r of antibiotics, both old and new. This a p p r o a c h avoids the p r o b l e m s of differences in laboratory m e t h o d ology, institution-associated resistance patterns, and other variables that arise w h e n agents are c o m p a r e d on the basis of p u b l i s h e d susceptibility data from different laboratories. Therefore, w e tested 100 consecutive P. aeruginosa isolated from the blood in patients from nine Pittsburgh hospitals against 19 a n t i p s e u d o m o n a l antibiotics.
From the VA Medical Center and University of Pittsburgh, Pittsburgh, PA. Address reprint requests to: Victor L. Yu, M.D., University of Pittsburgh School of Medicine, Scaife 968, Pittsburgh, PA 15261. Received September 24, 1986; revised and accepted January 29, 1987.
© 1987 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Avenue, New York, NY 10017
0732-8893/87/$03.50
108
J. Korvick et al.
MATERIALS AND METHODS Organisms One hundred consecutive P. aeruginosa blood isolates were obtained from patients hospitalized from 1983 to 1984 at the following Pittsburgh hospitals: VA Medical Center, Presbyterian University Hospital, Allegheny General Hospital, Mercy Hospital, Montefiore Hospital, Shadyside Hospital, St. Francis Hospital, Washington Hospital, and West Penn Hospital. ATCC 27853 was used as a control strain.
Antibiotics Reagent grade powders were supplied by the manufacturers. Each antibiotic powder was dissolved in sterile solutions as specified by the manufacturer to obtain a stock solution. Serial dilutions were then made with Mueller-Hinton broth (Difco, Detroit, MI), which was supplemented with 60 mg/L calcium and 20 mg/L magnesium.
In Vitro Susceptibility Testing An inoculum of each organism was prepared in trypticase soy broth and incubated for 4-6 hr to achieve log-growth-phase. Each sample was matched to a 0.5 MacFarland standard and diluted 1:200. Fifty microliters were placed in each well of two columns of a microtiter plate. The final concentration of the inoculum was approximately 5 x 10 s CFU/ml. Viable counts of the inoculum were performed using a spiral plate system (Spiral Systems Inc., Bethesda, MD). This device dispenses 40 ~L of inoculum on agar plates in spiral formation by logarithmic increments in volume. The plates were incubated 20 hr and counted. Minimum inhibitory concentrations (MIC) were determined with microtiter dilution techniques (Jones et al., 1985). Fifty microliters of supplemented Mueller-Hinton broth were added to each well of a sterile, 96-well microtiter plate (Flow Laboratories, McLean, VA). Fifty microliters of the working antibiotic solution were added to the first row of each column and serial twofold dilutions were then made with a sterile microdiluter (Titertek, Flow Labs, McLean, VA). These plates were placed in a humidified incubator for 20 hr at 37°C. The MIC endpoints were defined as the lowest antibiotic concentration providing a clear well for visual inspection. Minimum bactericidal concentrations (MBC) were performed in concert with the MICs. Ten microliter aliquots were removed from each of the last three wells of a column showing no growth and placed onto agar based medium. These plates were incubated at 37°C for 20 hr before reading. MBCs were defined as the concentration of the antibiotic which provided 99.9% kill. Each set of MIC/MBCs were performed in duplicate on different days.
RESULTS Table 2 shows the cumulative susceptibilities for each antibiotic. One hundred percent of isolates were susceptible to imipenem, whereas, 98% were susceptible to apalcillin, and 97% were susceptible to cefsulodin and cefpiramide. Although the MIC9o for tobramycin was >256 mg/L, the distribution was bimodal; 88% of the isolates were sensitive to tobramycin at MICs of 4 mg/L or less. Of the 100 P. areuginosa blood isolates, 12% were tobramycin-resistant. All of the tobramycin-resistant isolates were susceptible to apalcillin, azlociUin, aztreonam, cefsulodin, ceftazidime, ciprofloxicin, and imipenem. Two isolates were resistant in
Antibiotic Susceptibilities of P. Aeruginosa
109
TABLE 1. MICs and MBCs of 100 P s e u d o m o n a s aeruginosa Blood Isolates Using 19 A n t i p s e u d o m o n a l Agents, Old a n d New Antibiotic
MICso
MICgo
Ceftazidime Cefsulodin Cefpiramide° Cefoperazone Cefpirome (HR810)a Cefpimazole a
4 4 4 8 16 16
Apalcillin° Piperacillin Azlocillin Ticarcillin Mezlocillin Carbenicillin
2 8 8 32 64 64
8 16 32 128 128 128
Tobramycin Amikacin Gentamicin Netilmicin
2 8 4 16
>256 16 32 32
0.5 1 8
2 4 16
Range
MBCso
MBCgo
Range
4 8 8 16 32 32
16 128 32 128 64 128
1->256 1-128 1->128 4->512 4-256 2-<512
8 8 16 32 64 128
32 64 128 128 256 512
1-512 1->512 4->512 8->1024 32->1024 8->512
2 16 8 32
256 32 >256 64
0.5->512 1->64 2->1024 <0.06->256
1 2 8
2 8 32
Cephalosporins 16 16 16 32 32 64
0.5-128 1-128 1->512 1->512 4-256 2->512
Antipseudomonal Penicillins 0.5-512 1->512 2->512 0.5->1024 8->1024 8->512
Aminoglycosides 0.13-512 1-64 1->1024 <0.06->256
Others Ciprofloxacin ° Imipenem Aztreonama
<0.06-4 0.5-8 0.5-128
<0.06->8 0.5->16 1-128
aInvestigational.
vitro to all B-lactam antibiotics but sensitive to all aminoglycosides. Results of MIC/ MBC testing are s h o w n in Table 1. Tolerance, as defined by a MBCgo/MICgo ratio of >32 was not seen for any agent (Thrupp, 1986). DISCUSSION We sought to compare newer a n t i p s e u d o m o n a l agents with older established agents using recent (1983-1984) clinical blood isolates. The isolates were taken from n i n e Pittsburgh hospitals i n c l u d i n g a university referral hospital, a county general hospital, a VA hospital, and c o m m u n i t y hospitals; these hospitals provide a diverse source of organisms. We caution that the use of the MIC and/or MBC alone is inadequate for evaluating antibiotic potency. The inhibitory quotient (Ellner and Neu, 1981), a ratio of peak serum concentration of antibiotic to MIC, has also been used for antibiotic comparison. Using this ratio, i m i p e n e m , aztreonam, and cefpiramide appear to have the highest values. However, this ratio fails to take into account other factors, e.g., degree of protein binding, pH, penetration of antibiotic into target tissue, the area u n d e r the serum concentration time curve measuring total time of exposure of the organism to a given agent ("area u n d e r the curve"}. Nevertheless, this comprehensive study per-
110
J. K o r v i c k et al.
TABLE 2. C u m m u l a t i v e S u s c e p t i b i l i t i e s of 100 P s e u d o m o n a l B l o o d I s o l a t e s to 19 Antipseudomonal Antibiotics Cumulative percentage of isolates inhibited at dose (mg/L) Antibiotic
~0.5
1
2
8 3 2 1
42 28 15 2
4
8
16
32
64
128
9256
Susceptible (°/o)a
99 99 99 94 99 91
100 100 100 98
100 100 100
88 97 97 85 94 67
93 96 93 92
100 100 100 100 100 100
98 90 92 44 6 92
89
100
88 95 56 5
Cephalosporins Ceftazidime Cefsulodin Cefpiramide Cefoperazone Cefpirome Cefpimazole
1
Apalcillin PiperaciUin Azlocillin Ticarcillin Mezlocillin Carbenicillin
1
Tobramycin Amikacin Gentamicin Netilmicin
18
Ciprofloxacin Imipenem Az~eonam
56 12 1
7
71 73 55 18 7 16
88 88 85 66 33 35
94 97 94 85 79 67
97 98 97 93 94 89
96
Antipseudomonal Penicillins 13 1
59 2
87 43 14
1
94 79 57 2 1 1
98 90 85 44 6
99 93 92
97
77
89 79 57
32 10
Aminoglycosides 49 1 2
78 4 17 3
88 32 56 5
87 54
97 88 7
100 98 49
1
68 84 26
95 89 72
100 90 93
91 99
100 100
Others 100 74
91
96
99
100
87 100 74
°Isolates were considered susceptible if MIC was: ~1 for ciprofloxacin; ~4 for gentamicin, tobramycin, netilmicin; ~<8 for aztreonam, ceftazidime, imipenem; ~<16 for cefsulodim, cefoperazone, cefpimazole, piperacillin, ticarcillin, mezlocillin, apalcillin, amikacin; ~<32 for cefpiramide, cefpirome; ~64 for azlocillin; ~<128 for carbenicillin.
f o r m e d in o n e l a b o r a t o r y for 100 c o n s e c u t i v e b l o o d i s o l a t e s p r o v i d e s d a t a t h a t c a n be u s e d d i r e c t l y or i n c a l c u l a t i o n s for f u r t h e r c o m p a r i s o n s . In c o n c l u s i o n , w e s h o w t h a t t h e s e n e w e r a g e n t s are q u i t e p o t e n t i n v i t r o a g a i n s t P. aeruginosa a n d w o u l d a p p e a r to h a v e c o n s i d e r a b l e p o t e n t i a l i n t h e c l i n i c a l arena. F u r t h e r trials i n ill s u b j e c t s w i l l u l t i m a t e l y d e t e r m i n e t h e efficacy of e a c h agent.
REFERENCES Baltch AL, Griffin P (1977) Fseudomonas aeruginosa bacteremia: A clinical study of 75 patients. Am J Med Sci 274:119. Ellner P, Neu H (1981) The inhibitory quotient, a method for interpreting minimum inhibitory concentration data. J Am Med Assoc 246:1575. Flick MR, Cluff LE (1976) Pseudomonas bacteremia, a review of 180 cases. Am J Mad 60:501. Jones RN, Barry AL, Gavan TL, Washington JA (1985) Susceptibility tests: Microdilution and macrodilution broth procedures. In: Manual of Clinical Microbiology, 4th ed. Eds., Lennette EH, Balows A, Hausler WJ, Shadomy HJ. Washington, DC: American Society for Microbiology, pp. 972-977. Tapper M, Armstrong D (19741 Bacteremia due to Pseudomonas aeruginosa complicating neoplastic disease: A progress report. J Infect Dis 130(suppl):514.
Antibiotic Susceptibilities of P. Aeruginosa
111
Thrupp L (1986) Susceptibility testing of antibiotics in liquid media. In: Antibiotics in Laboratory Medicine, 2nd ed. Ed., Lorian V. Baltimore, MD: Williams & Wilkins, pp. 93-150. Van der Auwera P, Schuyteneer F (1983) In vitro susceptibility of Pseudomonas aeruginosa to old and new beta lactam antibiotics and aminoglycosides. J Antimicrob Chemother 11:511. Yu VL, Vickers RM, Zuravleff J] (1980) Comparative susceptibilities to moxalactam and eight other antipseudomonal antimicrobial agents (old and new). Antimicrob Agents Chemother 17:96.