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Antimicrobial Agents and Chemotherapy, June 1999, p. 1379-1382, Vol. 43, No. 6
Division of Infectious Diseases, Beth Israel
Deaconess Medical Center, and Harvard Medical School, Boston,
Massachusetts
Received 24 November 1998/Returned for modification 13 January
1999/Accepted 17 March 1999
Pseudomonas aeruginosa is a leading cause of nosocomial
infections. The risk of emergence of antibiotic resistance may vary with different antibiotic treatments. To compare the risks of emergence
of resistance associated with four antipseudomonal agents, ciprofloxacin, ceftazidime, imipenem, and piperacillin, we conducted a
cohort study, assessing relative risks for emergence of resistant P. aeruginosa in patients treated with any of these drugs.
A total of 271 patients (followed for 3,810 days) with infections due to P. aeruginosa were treated with the study agents.
Resistance emerged in 28 patients (10.2%). Adjusted hazard ratios for
the emergence of resistance were as follows: ceftazidime, 0.7 (P = 0.4); ciprofloxacin, 0.8 (P = 0.6); imipenem, 2.8 (P = 0.02); and piperacillin, 1.7 (P = 0.3). Hazard ratios for emergence of resistance
to each individual agent associated with treatment with the same agent
were as follows: ceftazidime, 0.8 (P = 0.7); ciprofloxacin, 9.2 (P = 0.04); imipenem, 44 (P = 0.001); and piperacillin, 5.2 (P = 0.01). We concluded that there were evident differences among
antibiotics in the likelihood that their use would allow emergence of
resistance in P. aeruginosa. Ceftazidime was associated with the lowest risk, and imipenem had the highest risk.
Pseudomonas aeruginosa is
a leading cause of nosocomial infections, ranking second among the
gram-negative pathogens reported to the National Nosocomial Infection
Surveillance System. There are a limited number of antimicrobial agents
with reliable activity against P. aeruginosa, including
antipseudomonal penicillins and cephalosporins, carbapenems, and
fluoroquinolones, particularly ciprofloxacin. Aminoglycosides are
frequently used as part of combination regimens for treatment of
serious pseudomonal infections but are generally not recommended as
single drugs. For each of these agents, emergence of resistance during
therapy has been described and has been recognized as a cause of
treatment failure (4, 6, 8, 10, 12, 13). Yet comparative
analyses of the frequency of emergence of resistance associated with
different classes of antipseudomonal drugs are lacking, even though
knowledge about the relative risks of emergence of resistance with
different antibiotics could be useful in helping to guide therapeutic
choices. Ideally, the information regarding risks of emergence of
resistance associated with individual regimens should come from a
large-scale prospective randomized study with multiple treatment
groups. Unfortunately, the costs associated with such a study would be
prohibitive. Therefore, we performed an observational study to compare
the relative risks for emergence of resistant P. aeruginosa
associated with four individual antipseudomonal agents.
In order to directly compare the overall effect of each antibiotic, we
examined emergence of resistance to any antipseudomonal antibiotic. In a secondary analysis, individual antibiotic
resistances were studied as separate and distinct endpoints,
focusing on the association between emergence of resistance to a
specific agent and exposure to that agent.
Hospital setting, data collection, and microbiology.
The
Deaconess Hospital is a 320-bed urban tertiary-care teaching hospital
in Boston, Mass. It utilizes 24 intensive-care unit (ICU) beds and has
approximately 11,000 patients admitted per year.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Emergence of Antibiotic-Resistant Pseudomonas
aeruginosa: Comparison of Risks Associated with Different
Antipseudomonal Agents
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Definitions and study design. Four antipseudomonal drugs used frequently in our hospital were studied: ceftazidime, ciprofloxacin, imipenem, and piperacillin. Piperacillin-tazobactam was used infrequently for treating pseudomonal infections and was grouped with piperacillin.
Criteria for entry into the study population were as follows: (i) admission between 1 August 1994 and 31 July 1996 with a hospital stay of at least 2 days; (ii) recovery of P. aeruginosa from clinical culture; (iii) susceptibility of the first pseudomonal isolate to at least one of the four antibiotics listed above; (iv) subsequent treatment with at least one of these drugs; and (v) confirmation of clinical infection on the basis of Centers for Disease Control and Prevention definitions for infection (modified to include community infections and with exclusion of asymptomatic bacteriuria) (7). The patients were followed from the date of detection of their baseline isolate until discharge or until the detection of the emergence of resistance in a subsequent clinical isolate of P. aeruginosa. The emergence of resistance to individual antibiotics was also studied. Patients were included in each of these analyses according to the susceptibility of their baseline isolate to the study drug. The follow-up periods were defined as described above, except that the endpoint was considered to be the emergence of resistance to the specific antibiotic that defined the cohort; e.g., for the cohort defined by baseline susceptibility to ceftazidime, the outcome was the emergence of resistance to ceftazidime. The MICs determining susceptibility thresholds for the different drugs were as follows:
64 µg/ml for piperacillin, <16 µg/ml for
ceftazidime, < 8 µg/ml for imipenem, and < 2 µg/ml for
ciprofloxacin. Isolates with intermediate susceptibility were
considered resistant in order to match better treatment decisions in
clinical settings. The emergence of resistance was defined as the
clinical detection of resistant P. aeruginosa with a minimum
fourfold increase (two dilutions) in MIC compared to that of the
baseline isolate (the first isolate for each admission), which resulted
in a change in the interpretive criteria.
To explore confounding factors, the following variables were analyzed
in addition to the study drugs: age, gender, underlying diseases and
weighted comorbidities (Charlson comorbidity score) (3),
culture site, surgical procedures, ICU stays, time interval between
hospital admission and the detection of the baseline isolate, number of
initial antibiotic resistances in the baseline isolate, average number
of nursing hours per day (calculated from nursing administrative
records), administration of more than one study drug, and concomitant
administration of aminoglycosides. A score was constructed in order to
adjust for the intensity of clinical culturing by calculating the
average number of cultures obtained per day during the follow-up period.
All available pairs of isolates from patients in whom resistance
emerged were studied by pulsed-field gel electrophoresis (PFGE) as
previously described (5). Isolates from before and after the
emergence of resistance were compared.
Statistical analysis. Statistical analyses were performed with SAS (SAS Institute Inc., Cary, N.C.) and Stata (Stata Corp., College Station, Tex.) software. Survival analysis was performed in order to allow for different follow-up periods.
Crude and multivariable Cox proportional-hazard models were used to address the emergence of resistance. Thus, for each day of follow-up, comparisons were made only among individuals who were still in the hospital on that day. Treatment courses with the study antibiotics were analyzed as time-dependent variables. The measure of relative risk in Cox proportional-hazard regression is the hazard ratio (HR), which in this study represents the risk ratio per unit of time for emergence of resistance, comparing "exposed" and "unexposed" patients (e.g., patients who received ceftazidime versus patients who did not receive ceftazidime). Variables with a P value of <0.2 in the crude analysis were considered candidates for multivariable analysis and added to a model that included the study drugs. In addition, variables were tested for confounding by adding them one at a time to the model and examining their effects on the beta coefficients of the study drugs. Variables which caused substantial confounding (a change in the beta coefficient of greater than 10%) were included in the final model. Effect modification between antibiotics was examined by using interaction terms. The proportional-hazard assumption was tested for every analyzed variable. All statistical tests were two tailed. A P value of <0.05 was considered significant.| |
RESULTS |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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Emergence of resistance (to any of four antipseudomonal drugs). Two hundred and seventy-one patients satisfied the criteria for entry in the study cohort; 162 were males. The single most common site of infection was a wound. The average age of the patients was 62 (range, 24 to 94). The susceptibility pattern of the baseline isolates was as follows: 15 (5%) were resistant to piperacillin, 19 (7%) were resistant to ceftazidime, 36 (13%) were resistant to imipenem, and 58 (21%) were resistant to ciprofloxacin. One hundred and eighty-five (68%) of the baseline isolates were susceptible to all four study drugs, 56 (20%) were resistant to one agent, 27 (10%) were resistant to two agents, and 6 (2%) were resistant to three agents. The patients were followed for a total of 3,810 days. The median follow-up period was 11 days (range, 2 to 72 days). The number of patients receiving each of the study antibiotics was as follows: imipenem, n = 37 (14%); ciprofloxacin, n = 98 (36%); piperacillin, n = 91 (33%); ceftazidime, n = 125 (46%). Sixty-six patients received more than one study agent. Seventy-seven patients received an aminoglycoside in addition to a study agent. The median duration of aminoglycoside therapy was 6 days.
P. aeruginosa resistant to at least one of the study agents emerged in 28 patients (10.2%), an incidence of 7.4 per 1,000 patient-days. Pairs of isolates (before and after resistance emerged) from nine of these patients were available and were typed by PFGE. Typing patterns before and after the emergence of resistance were identical in each of the patients, confirming that resistance emerged in a susceptible isolate. The median time to emergence of resistance was 14 days (range, 2 to 65 days). Characteristics and exposures in these patients are summarized in Table 1 along with HRs. Imipenem treatment was associated with a 2.9-fold-higher hazard of emergence of resistance. In the crude analysis, other factors significantly associated with emergence of resistance were the frequency of microbiological culturing and the length of the hospital stay before entry into the cohort.
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DISCUSSION |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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Resistance to antimicrobial agents is an increasing clinical problem and is a recognized public health threat. P. aeruginosa shows a particular propensity for the development of resistance. The emergence of resistance in P. aeruginosa also limits future therapeutic choices and is associated with increased rates of mortality and morbidity and higher costs (2, 8). Therefore, we conducted this study to assess resistance arising during treatment with different antibiotics, first by examining the overall effect of each antibiotic on emergence of resistance and second by examining the emergence of resistance to individual agents.
We found that emergence of resistance to at least one antibiotic occurred in 10.2% of the patients (7.4 cases per 1,000 patient-days). This proportion should be considered a minimum estimate of the risk of emergence of resistance during antipseudomonal therapy, since it is based solely on clinical cultures and includes follow-up only during the index hospitalization. Resistance emerged during treatment with each class of antibiotic and did not appear to be significantly prevented by the use of combination therapy with aminoglycosides. However, the latter issue needs to be further examined in studies that include larger number of patients on aminoglycosides.
Important differences between antibiotics were evident. First, imipenem was associated with a significantly higher overall risk of emergence of resistance (HR, 2.8; P = 0.02) and had the strongest association with emergence of resistance to itself in the analysis of individual antibiotics (HR, 44; P = 0.001). In contrast, ceftazidime had the lowest risk for emergence of resistance in the combined analysis (HR, 0.7), and showed no association with emergence of resistance to itself (i.e., to ceftazidime) (HR, 0.8; P = 0.7). The relative risk for ciprofloxacin in the combined analysis was also low, but in contrast to ceftazidime, ciprofloxacin was distinctly associated with emergence of resistance to itself (HR, 9.2; P = 0.04).
The finding that imipenem carries a higher risk of emergence of pseudomonal resistance is consistent with the results of other studies. The clinical emergence of resistant P. aeruginosa has been described during imipenem therapy, ranging from 14 to 53% and occasionally leading to treatment failures (4, 6, 9, 13, 14). In two randomized clinical trials, these rates were significantly higher for imipenem than for ciprofloxacin or piperacillin-tazobactam (6, 9). Moreover, imipenem resistance in P. aeruginosa became widespread in some hospitals soon after the introduction of this agent (1). In this study more patients with P. aeruginosa infections were included than in the randomized trials, and adjustment for possible confounding was performed. Moreover, this study allowed direct comparison of four different antipseudomonal agents while accounting for differences in follow-up periods by using survival analysis. Although treatment with imipenem could result more often in the emergence of resistant P. aeruginosa than treatments with other antipseudomonal agents, this tendency may not translate into a higher prevalence of imipenem resistance among hospital isolates. Ciprofloxacin resistance, for instance, is more common than imipenem resistance in P. aeruginosa isolated from inpatients at our institution (15 versus 9%) (14). This apparent discrepancy might be related to differences in the frequency of use of various agents and to the different likelihoods of persistence of resistant strains.
An observational study such as this has a number of limitations, including the potential for confounding due to the lack of randomization and the use of more than one study antibiotic in some patients. However, multivariable analysis allowed us to adjust for confounding variables and to assess the independent effects of each antibiotic.
Follow-up was continued only during the hospital stay, and not until the resolution of infection. We used survival analysis to avoid the potential bias relating to differences in follow-up. Using these methods, the risks for patients with the same follow-up were compared to each other. All of the patients had follow-up cultures, but the frequency of culturing differed among patients. Although we adjusted for the differences in culturing density by adjusting for the culturing score, the confounding related to it may not have been fully controlled for. Our study also did not specifically address the mechanisms by which resistance occurred (11). We typed only a limited number of organisms by PFGE to show that resistance emerged in a susceptible strain. Knowledge of the specific means by which resistant microorganisms emerge is likely to be useful for designing effective prevention measures.
One should always remember that the spread of resistant organisms from patient to patient can be reduced by appropriate infection control measures. The results of this study are not generalizable to organisms other than P. aeruginosa. In other gram-negative pathogens, such as Enterobacter spp., emergence of resistance to broad-spectrum cephalosporins, including ceftazidime, may occur frequently, while resistance to imipenem is extremely rare.
In conclusion, the present study is important from a practical point of view. We believe that the use of imipenem for treatment of P. aeruginosa should be reserved for situations where the infection is polymicrobial, particularly when anaerobic bacteria are present, or for pseudomonal isolates resistant to other antibiotics. In cases where imipenem is selected as the antipseudomonal antibiotic, the potential for emergence of resistance should be anticipated, and in appropriate circumstances, routine culturing and susceptibility testing should be performed to detect the emergence of resistance P. aeruginosa as soon as possible.
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FOOTNOTES |
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* Corresponding author. Mailing address: Division of Infectious Diseases, Tel Aviv Medical Center, 6 Weizman St., Tel Aviv 64239, Israel. Phone: (972) 3 697-3317. Fax: (972) 3 697-4996. E-mail: ycarmeli{at}mailexcite.com.
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REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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|---|
| 1. | Basustaoglu, A. C., H. Gun, M. A. Saracli, M. Baysallar, and T. Haznedaroglu. 1995. Development of resistance to imipenem among nosocomial isolates of Pseudomonas aeruginosa. Eur. J. Clin. Microbiol. Infect. Dis. 14:469-470[Medline]. |
| 2. | Carmeli, Y., N. Troillet, A. W. Karchmer, and M. H. Samore. Pseudomonas aeruginosa: health and economic impact of antibiotic resistance and emergence of resistance. Arch. Intern. Med., in press. |
| 3. | Charlson, M. E., P. Pompei, K. L. Ales, and C. R. McKenzie. 1987. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40:373-383[Medline]. |
| 4. |
Cometta, A.,
J. D. Baumgartner,
D. Lew,
W. Zimmerli,
D. Pittet,
P. Chopart,
U. Schaad,
C. Herter,
P. Eggimann,
O. Huber, et al.
1994.
Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients.
Antimicrob. Agents Chemother.
38:1309-1313 |
| 5. | D'Agata, E. L., L. Vekataraman, P. DeGirolami, and M. Samore. 1997. Molecular epidemiology of ceftazidime-resistant gram-negative bacilli in a nonoutbreak setting. J. Clin. Microbiol. 35:2602-2605[Abstract]. |
| 6. |
Fink, M. P.,
D. R. Snydman,
M. S. Niederman,
K. V. Leeper, Jr.,
R. H. Johnson,
S. O. Heard,
R. G. Wunderink,
J. W. Caldwell,
J. J. Schentag,
J. A. Siami,
R. L. Zameck,
D. C. Haverstock,
H. H. Reinhart, and R. M. Echols.
1994.
Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastin.
Antimicrob. Agents Chemother.
38:547-557 |
| 7. | Garner, J. S., W. R. Jarvis, T. G. Emori, T. C. Horan, and J. M. Hughes. 1988. CDC definitions for nosocomial infections, 1988. Am. J. Infect. Control 16:128-140[Medline]. |
| 8. | Harris, A., C. Toress-Vierra, L. Ventakataraman, P. C. DeGirolami, M. H. Samore, and Y. Carmeli. Epidemiology and clinical outcomes of infections with multi-resistant Pseudomonas aeruginosa. Clin. Infect. Dis., in press. |
| 9. |
Jaccard, C.,
N. Troillet,
S. Harbarth,
G. Zanneti,
D. Aymon,
R. Schneider,
R. Chiolero,
B. Ricou,
J. Romand,
O. Huber,
P. Ambrosseti,
G. Praz,
D. Lew,
J. Bille,
M. P. Glauser, and A. Commeta.
1998.
Prospective randomized comparison of imipenem-cilastin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis.
Antimicrob. Agents Chemother.
42:2966-2972 |
| 10. | Milatovic, D., and I. Braveny. 1987. Development of resistance during antibiotic therapy. Eur. J. Clin. Microbiol. 6:234-244[Medline]. |
| 11. | Miro, E., F. Navarro, F. March, F. Sanchez, and B. Mirelis. 1995. Emergence of different resistance mechanisms in Pseudomonas aeruginosa in a patient treated with imipenem. Eur. J. Clin. Microbiol. Infect. Dis. 14:731-732[Medline]. |
| 12. |
Pechere, J. C., and I. R. Vladoianu.
1992.
Development of resistance during ceftazidime and cefipime therapy in a murine peritonitis model.
J. Antimicrob. Chemother.
29:563-573 |
| 13. | Quinn, J. P., E. J. Dudek, C. A. DiVincenzo, D. A. Lucks, and S. A. Lerner. 1986. Emergence of resistance to imipenem during therapy of Pseudomonas aeruginosa infections. J. Infect. Dis. 154:289-294[Medline]. |
| 14. | Troillet, N., M. H. Samore, and Y. Carmeli. 1997. Imipenem-resistant Pseudomonas aeruginosa: risk factors and antibiotic susceptibility pattern. Clin. Infect. Dis. 25:1094-1098[Medline]. |
Antimicrobial Agents and Chemotherapy, June 1999, p. 1379-1382, Vol. 43, No. 6
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[Full Text] -
Lynch, J. P. III
(2001). Hospital-Acquired Pneumonia : Risk Factors, Microbiology, and Treatment. Chest
119: 373S-384S
[Abstract] [Full Text] -
(1999). Pseudomonas Aeruginosa Develops Resistance to Imipenem. JWatch Infect. Diseases
1999: 7-7
[Full Text] -
Tranier, S., Bouthors, A.-T., Maveyraud, L., Guillet, V., Sougakoff, W., Samama, J.-P.
(2000). The High Resolution Crystal Structure for Class A beta -Lactamase PER-1 Reveals the Bases for Its Increase in Breadth of Activity. J. Biol. Chem.
275: 28075-28082
[Abstract] [Full Text]
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