Scand J Infect Dis 24: 233-240, 1992
CASE REPORT
Enterobacter Endocarditis ALLAN R. TUNKEL', MICHAEL J . FISCH', ANDREW SCHLEIN2 and w . MICHAEL SCHELD~
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From the Division of lnfectious Diseases and Department of Internal Medicine, 'Medical College of Pennsylvania, Philadelphia, Pennsylvania, and >University of Virginia School of Medicine, Charlottesville, Virginia, USA Endocarditis due to Enterobacter species is very rare. We recently cared for a patient who developed E. cloacae endocarditis following mitral valve replacement with a porcine heterograft, and was successfully treated with antibiotic therapy alone. A review of the literature disclosed an additional 17 well-described cases of enterobacter endocarditis. Two-thirds of the patients had underlying cardiac disease. The mitral valve was most frequently involved (10116 cases) with 4 of the patients having concomitant aortic valve involvement. The overall mortality rate was 44.4%. Antibiotic therapy of enterobacter endocarditis should consist of the combination of a beta-lactam antibiotic and an aminoglycoside with careful monitoring of blood cultures to assure the adequacy of therapy. Resistance of enterobacter to previously susceptible antibiotics may occur during therapy due to induction of a chromosomallymediated beta-lactamase, necessitating a change in antimicrobial therapy. Valvular surgery is indicated for patients failing medical management. A . R. Tunkel, MD, PhD, Division of Infectious Diseases, Medical College of Pennsylvania, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129, USA
INTRODUCTION Endocarditis due to Gram-negative bacilli is unusual despite the high incidence of Gramnegative bacteremia associated with manipulation and infection of the genitourinary and intestinal tracts. Of 452 valvular infections reported in the 1960s, only 1.7% were caused by Gram-negative organisms (1) versus 7% in more recent series (2). The incidence of Gramnegative endocarditis is higher in prosthetic valve endocarditis, accounting for about 20% of cases of early and 10-14% of cases of late prosthetic valve endocarditis (3-5). Increases in the incidence of Gram-negative endocarditis are due, in part, to the advent of antibiotics which select out for resistant Gram-negative organisms, immunosuppressive therapy, cardiac valve replacement, and the increased frequency of intravenous drug abuse (2). Among the Gram-negative bacilli, endocarditis due to Enterobacter species is very rare. We recently cared for a patient with endocarditis due to Enterobacter cloacae following mitral valve replacement with a porcine heterograft. Here we discuss this case and review the literature on this entity. CASE REPORT The patient was a 57-year-old female with a long history of rheumatoid arthritis and chronic obstructive pulmonary disease who was diagnosed with non-Hodgkin's lymphoma 1.5 years prior to entry. She went into a complete remission following therapy with cyclophosphamide, etoposide, vincristine, S-fluorouracil. adriamycin, and dexamethasone. She did well until 1 week before admission when she presented
234 A . R. Tunkel el al.
Scand J lnfect Dis 24
Table I. Clinical characteristics of patients with enterobacter endocarditis
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Case Age Sex no.
Valve involved
Underlying cardiac disease
Underlying conditions
Antibiotic therapy
Outcome
Ref. no.
Streptomycin, No sulfadiazine Penicillin, s t r e p N o tomycin
Survived Died
6
No
Died
8
Died
9
Died
10
Died
11
Survived
12
No
Died
13
No
Survived Survived
13
Died
15
1
28
M
Mitral
No
I.v. drug use
2
65
M
Aortic
?Rheumatic heart disease
3
22
F
Mitral
No
4
-
Tricuspid
5
-
Mitral
?Valve trauma secondary to pulmonary hypertension Prosthetic valve
Prostatic hypertrophy, transurethral resection of prostate, prostatic abscess Ureteral calcuPenicillin, streplus, cysto5copy tomycin, sulfadiazine, sulfawith meatomy thiazole, bacterioph age, polymyxin Pulmonary arteriosclerosis
6
48
M
Aortic. mitral
No
I.v. drug abuse
7
54
M
Aortic, mitral
Prosthetic valve
Urinary tract infection
-
Rheumatic heart disease Ventricular septa1 defect Congenital aortic stenosis, cornmissurotomy Rheumatic heart disease, mitral annuloplasty No I.v. drug abuse
8
3.5 M
9
8
F
-
10
13
F
Aortic
11
32
F
Aortic, mitral
12
52
M
Tricuspid
13
24
M
Tricuspid
14
30
M
15
28
M
Aortic, mitral Tricuspid
16
-
17
41
18
57
I.v. drug abuse, pulmonary embolus Rheumatic heart I.v. drug abuse disease I.v. drug abuse No
Mitral
Prosthetic valve (porcine)
M
Mitral
F
Mitral
Prosthetic valve (porcine) Prosthetic valve (porcine)
Rheumatoid arthritis, nonHodgkin’s lymphoma
Surgical therapy
Met hicillin, No chloramphenicol, erythromycin No Kanamycin, gentamicin, chloramphenicol ChloramphenNo icol, kanamycin, cephalothin
No Carbsnicillin. probenecid, kanamycin Chloramphenicol Yes
7
14
Chloramphenicol, streptomycin Nafcillin
No
Survived
16
No
Survived
16
Penicillin, streptomycin Oxacillin, cefanone, gentamicin Cephalothin, carbenicillin, gentamicin Tobramycin, gentamicin Ceftazidime, gentamicin
No
Survived Survived Survived
17
No
Died
20
No
Survived
Present case
Yes Yes
18 19
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Enlerobacter endocarditis 235
to an outside hospital with the acute onset of shortness of breath. Examination revealed that the patient was febrile to 38.8"C. markedly dyspneic, and was in congestive heart failure with a new mitrat regurgitation murmur. Myocardial infarction was ruled out by normal cardiac enzymes. One of 4 blood cultures grew Staphylococcus aureus and she was treated with intravenous (i-v.)nafcillin. However, the patient became hemodynamically unstable and was transferred to the University of Virginia Health Sciences Center where a cardiac catheterization revealed 4+ mitral regurgitation, a mild reduction in left ventricular function, and normal coronary artery anatomy. The patient underwent mitral valve replacement with a 25 mm-Hancock porcine valve prosthesis. Pathologic examination of the native valve revealed multiple chordae tendonae ruptures and a myxamatous mitral valve without evidence of endocarditis. Nafcillin was discontinued after a 14-day course. Her postoperative course was complicated by prolonged intubation, congestive heart failure, bronchospasm, and upper gastrointestinal hemorrhage. One week after the nafcillin was discontinued, the patient developed a cellulitis on the right forearm and intravenous cefazolin was begun. Over the next several days she began to improve, was extubated, and remained hemodynamically stable. Cardiac examination was normal without evidence of murmurs. Five days later, the patient spiked at temperature to 39.6"C accompanied by shaking chills. The pulse was 120 beatshin. respiratory rate 24/min, and blood pressure llOn0 mmHg. Examination revealed a few bibasilar crackles and a new grade III/VI holosystolic murmur best heard at the apex and radiating to the axilla. Four of 4 blood cultures obtained over a time period of 48 h grew Enterobacter cloacae and a central line catheter tip yielded 50 colony-forming units of the same microorganism. The minimal inhibitory concentration for ceftazidime was 1 mg/l. gentamicin 1 mg/l. piperacillin 16 mg/l and imipenem > 16 mg/l. Ceftazidime (2 g i.v. every 8 h) and gentamicin (50 mg i.v. every 24 h) were begun. Cardiac echocardiography showed a normal valve prosthesis with trace mitral regurgitation. Cardiac catheterization revealed a normal functioning prosthesis with a 1+ periprosthetic leak. It was felt that she would not be a good surgical candidate. The patient'scondition stabilized on antibiotic therapy. The trough serum bactericidal titer, measured by the guidelines of the National Committee for Clinical Laboratory Standards, was 1:256. Antimicrobial therapy was continued for 6 weeks. She remained afebrile without evidence of cardiac decompensation. Blood cultures remained negative 2 months after discontinuation of antibiotics. The patient was subsequently lost to follow-up.
MATERIALS A N D METHODS Cases of enterobacter endocarditis reported in the literature were identified using Index Medicus and by a literature search of the MEDLINE data base of the MEDLARS service, National Library of Medicine. Only English language articles were included. The references of these citations were reviewed in depth for additional cases. Reports that did not have in-depth case histories were not included in this review. To be part of this series, cases were required to contain information regarding cardiac valve involved, underlying conditions, medical and/or surgical therapy, and outcome. There were 17 well-described cases of enterobacter endocarditis in the literature from 1949 to 1990 (6-20). With the addition of our case, 18 cases were available for analysis (Table I). Some additional cases are alluded to in larger series, and some of the characteristics of these cases are described in the discussion.
RESULTS Enterobacter endocarditis occurred in 10 men and 5 women (gender not indicated in 3 cases). The average age was 33.7 years with a range of 3.545 years. The majority of the patients had mitral valve involvement (10 cases), including 4 cases with combined mitral and aortic valve involvement. All of the 5 cases of prosthetic valve involvement due to enterobacter occurred on prosthetic mitral valves. The majority of the patients (12/18) had underlying cardiac disease including the presence of prosthetic valves (5 cases), rheumatic heart disease (4 cases), valve trauma secondary to pulmonary hypertension (1 case), ventricular septa1 defect (1 case), and congenital aortic stenosis (1 case). Intravenous drug abuse accounted for 3 of the 4 cases of tricuspid valve endocarditis, 1 case on the mitral valve, and 2 cases of combined mitral and aortic valve endocarditis. The most common non-cardiac underlying condition was i.v. drug abuse (6 cases). Besides an enterobacter, other organisms were recovered in 2 cases. In patient 5, there
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Scand J Infect Dis 24
was concomitant endocarditis with S. aureus, Candida albicans, and Paracolobactrum aerogenes; in patient 14 with Enterococcus faecalis and the viridans streptococcus. Patients received a variety of antimicrobial agents with most regimens containing an aminoglycoside (Table I). Surgical therapy was performed in 3 cases with 2 of the patients surviving. The overall mortality rate was 44.4%, and was lower for right-sided (25%) as compared to left-sided (50%) enterobacter endocarditis in this series.
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DISCUSSION Many different bacterial organisms have been implicated in the causation of infective endocarditis. Streptococci and staphylococci account for 80-90% of cases. Although Gramnegative bacilli have been reported in a lower percentage of cases, it has become clear that the incidence of infective endocarditis due to these organisms has increased in recent years; 1.7% in the 1960’s (1) versus 7% in more recent series (2). Several explanations have been proposed to account for the lower incidence of Gram-negative, as opposed to Grampositive, endocarditis (2,21). These include the greater capacity of Gram-positive organisms (e.g. S. aureus) to adhere to valve leaflets (22), the lower frequency that Gram-negative bacteria are involved in transient bacteremias in healthy people (23), and that nonbacteremic isolates of Gram-negative bacteria are less resistant to serum bactericidal activity than Gram-positive organisms (24). In addition, Gram-negative bacteria are less able than Gram-positive cocci to induce endocarditis in an experimental rabbit model (25). In a review from the Mayo Clinic during the period 1958-1975, 56 cases of endocarditis due to Gram-negative bacilli were observed, most due to “fastidious” non-enteric organisms (26). The increased incidence of these organisms in infective endocarditis is due, in part, to the use of invasive diagnostic techniques, treatment with antibiotics, presence of cardiac prostheses, i,v. drug abuse, and improvement in microbiologic techniques (2). Gramnegative bacilli have accounted for about 20% of isolates in early and 1&14% of isolates in late prosthetic valve endocarditis (3-5). Among the Enterobacteriaceae, Salmonella species have accounted for the majority of isolates in early reports due to the affinity of these organisms for abnormal heart valves (27). In a review of 44 cases of endocarditis due to enteric Gram-negative bacilli other than salmonella (28), organisms identified were Escherichia coli (17 cases) Klebsiella-Enterobacter group (9 cases), Serratia marcescens (13 cases), Proteus and Providentia species (2 cases each), and Citrobacter (1 case). A recent increase in the frequency of endocarditis due to Pseudomonas aeruginosa has been observed, predominantly among patients who abuse i.v. drugs (29, 30). Enterobacter is a rare isolate in cases of Gram-negative endocarditis, accounting for only 6% of isolates in narcotic addict-associated Gram-negative endocarditis in one series (2). In our literature review, we could identify only 17 well-described cases. This low number may relate to the fact that the genus enterobacter was not defined as a separate entity until the 1960’s (31). Before then, the differentiation of enterobacter from klebsiella was not routinely performed, which led to the reporting of many infections being caused by the klebsiella-enterobacter group; organisms with this description were excluded from our analysis. Therefore, our selection of cases is biased since only those cases reported in the literature were available for review, and those cases may or may not be representative of all episodes of enterobacter endocarditis. Among the clinical characteristics of the 18 cases of enterobacter endocarditis described here (Table I), several points can be made. There was a wide variation in the age of the patients (3.5-65 years) with a mean of 33.7 years. Males outnumbered females in a ratio of 2: 1. The mitral valve was most frequently involved (10/16 cases) with 4 of the patients having
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Enterobacter endocarditis 231
concomitant aortic valve involvement. The tricuspid valve was affected in 4 cases, 3 of which occurred in intravenous drug abusers. Two-thirds of the patients had underlying cardiac disease including the presence of prosthetic valves, rheumatic heart disease, pulmonary hypertension, ventricular septa1 defect, or congenital aortic stenosis. Surgical.therapy was used only in 3 patients, 2 of whom survived. The overall mortality rate in our series was 44.4%. However, these data may be flawed because our series represents only welldescribed cases of enterobacter endocarditis. In a review of the Boston City Hospital experience with bacterial endocarditis from 1933-1965, 20 cases of endocarditis due to enterobacter were identified, although detailed information on these cases was not available (32); all the patients died. When combined with our data, the overall mortality rate for enterobacter endocarditis was 73.7%. Case fatality rates are likely much lower today with the availability of more effective antimicrobial therapy against Enterobacter species as well as valve replacement surgery for cases refractory to medical therapy. Mortality rates were lower for right-sided (25%) as compared to left-sided (50%) enterobacter endocarditis in our series. One patient with right-sided endocarditis underwent surgery with a positive result, and 2 patients with left-sided endocarditis had valve replacement, 1 of whom survived. The optimal management of enterobacter endocarditis remains unclear. In this series it is difficult to make specific antibiotic recommendations for the treatment of enterobacter endocarditis because the choice of a particular antimicrobial agent did not correlate with outcome. Therapy of enteric aerobic Gram-negative bacillary endocarditis should be guided by in vitro susceptibility testing and bactericidal synergy studies (33). The experimental rabbit model of infective endocarditis has been utilized to emphasize many of the therapeutic principles in the treatment of endocarditis due to these organisms (34). For example, the combination of carbenicillin plus gentamicin was more effective than either alone in the rabbit model of P. aeruginosa endocarditis (35). Similar results have been observed in the therapy of pseudomonas endocarditis in intravenous drug abusers (29, 36). Therefore, therapy should consist of a beta-lactam agent in combination with an aminoglycoside to which the organism displays in vitro susceptibility. Despite problems with interpretation, the therapy of aerobic Gram-negative endocarditis should be tailored to achieve trough serum bactericidal titers of at least 1:8 (37). The duration of therapy is controversial, but is usually continued 4-6 weeks. Repeat blood cultures are essential to delineate response to therapy because patients who fail to respond bacteriologically to medical management are candidates for surgical therapy. In practice, cure rates are better in patients with right-sided than left-sided Gram-negative endocarditis (21). A recent review has suggested that patients with left-sided endocarditis due to P. aeruginosa have a better chance for cure when treated with early valve replacement and appropriate antibiotics than when treated with antibiotics alone (30). In vitro susceptibility testing reveals that virtually all enterobacter strains are resistant to penicillin, ampicillin, erythromycin, clindamycin, vancomycin, and the sulfonamides (31, 38). The first generation cephalosporins also have little or no anti-enterobacter activity. Drugs with a moderate degree of in vitro activity include the second generation cephalosporins. trimethoprim-sulfamethoxazole, and the antipseudomonal penicillins. The third generation cephalosporins, imipenem, the aminoglycosides, and the quinolones have the highest in vitro activity. However, with widespread use of newer beta-lactam antibiotics, enteric Gram-negative bacilli including enterobacter have acquired the ability to develop resistance to these drugs (39). Shortly after cefamandole became available, reports of the emergence of resistance of Enterobacter species to the drug during therapy began to appear due to the presence of an inducible, chromosomally mediated beta-lactamase capable of inactivating cefamandole (40). There was also simultaneous development of cross-resistance to many of
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238 A. R. Tunkel et ai.
Scand J Infect Dis 24
the other new beta-lactam antibiotics including cefuroxime, third generation cephalosporins, monobactams, and broad-spectrum penicillins (39). Beta-lactamase induction with cefoxitin has been shown to confer resistance to ceftazidime (41). Two mechanisms have been proposed to account for the development of resistance in enterobacter isolates (39). The first mechanism, which produces multiple beta-lactam resistance, is the induction of chromosomal beta-lactamases that mediate resistance to nonsubstrate drugs by the creation of a nonhydrolytic barrier that blocks access to target proteins in the cell. In contrast to the newer cephalosporins, the activity of an antibiotic such as imipenem is unaffected by this beta-lactamase because imipenem, unlike most other beta-lactam agents, acts on penicillinbinding protein 2 which is present in low quantities within the cell as compared with the other lethal binding proteins (42, 43), and penetrates rapidly across the bacterial outer membrane, a property presumably related to its compact molecular structure (44). The second mechanism, which produces beta-lactadaminoglycoside resistance, involves a change in outer membrane permeability mediated by altered porin proteins (39). Based on the above observations, clinical failure of antimicrobial therapy against enterobacter isolates that have good initial in vitro susceptibilities may represent the emergence of multidrugresistant organisms. In these clinical situations, imipenem is the antimicrobial agent of choice. The quinolones may also be effective, although there is no clinical experience with the use of these agents in enterobacter endocarditis. Difloxacin has been shown to be significantly more effective than cefoperazone in the rabbit model of E. aerogenes endocarditis (45), and further studies may establish the effectiveness of the quinolones in this infection. There was no evidence of the development of resistance during therapy in our literature review of enterobacter endocarditis. In summary, we have described a case of enterobacter endocarditis and reviewed an additional 17 well-documented cases. Therapy of this infection should consist of the combination of a beta-lactam antibiotic and an aminoglycoside to which the organism displays good in vitro susceptibility with careful monitoring of blood cultures to assure the adequacy of therapy. Resistance of enterobacter to previously susceptible antibiotics may occur during therapy necessitating a change in antimicrobial therapy. Valvylar surgery is indicated for patients failing medical management. Further descriptions of cases of enterobacter endocarditis may aid in determining the optimal medical and surgical treatment of these patients.
ACKNOWLEDGMENTS We gratefully acknowledge Ms Mona Bernhardt and Ms Eve Lorraine Schwartz for secretarial assistance. This work was supported in part by a research grant (ROl-AI17904) and a training grant (T32-AI07046) from the National Institute of Allergy and Infectious Diseases. W. Michael Scheld is an established investigator of the American Heart Association.
REFERENCES 1. Pelletier LL, Petersdorf RG. Infective endocarditis: a review of 125 cases from the University of
Washington Hospitals, 1963-1972. Medicine 56: 287-313, 1977. 2. Cohen PS, Maguire JH, Weinstein L. Infective endocarditis caused by gram-negative bacteria: a review of the literature, 1945-1977. Prog Cardiovasc Dis 22: 205-242, 1980. 3. Watanakunakorn C. Prosthetic valve infective endocarditis. Prog Cardiovasc Dis 22: 181-192,1979, 4. Wilson WR, Danielson CK, Giuliana ER, Geraci 3E. Prosthetic valve endocarditis. Mayo Clin Proc 57: 155-161, 1982. 5. Karchmer AW. Treatment of prosthetic valve endocarditis. In: Sande MA, Kaye D, Root RK, eds. Endocarditis. New York: Churchill Livingstone, 165182, 1984. 6. Luttgens WF, Endocarditis in “main line” opium addicts. Arch Intern Med 83: 6 5 M 6 4 , 1949.
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Enterobacter endocarditis 239
7. Sussman LN, Cohen I, Freund AJ. Acute Aerobacter aerogenes endocarditis complicating genitourinary tract infection. NY State J Med 50: 583-586, 1950. 8. Wallace CS. Bacterial endocarditis with emphasis on the Escherichia-Aerobacter group as the causative agent: report of a fatal case. Ann Intern Med 34: 1463-1472, 1951. 9. Bashour FA, Winchell CP. Right-sided bacterial endocarditis. Am J Med Sci 240: 411416, 1960. 10. Stein PD, Harken DE, Dexter L. The nature and prevention of prosthetic valve endocarditis. Am Heart J 71: 393407, 1966. 11. Ramsey RG, Gunnar RM, Tobin JR Jr. Endocarditis in the drug addict. Am J Cardiol25: 608-618. 1970. 12. Yeh TJ, Anabtawi IN, Cornett VE, White A, Stern WH, Ellison RG. Bacterial endocarditis following open-heart surgery. Ann Thorac Surg 3: 2 9 3 6 , 1967. 13. Caldwell RL, Hurwitz RA, Girod DA. Subacute bacterial endocarditis in children. Am J Dis Child 122: 312-315, 1971. 14. Lere RJ. Postoperative endocarditis due to Enterobacter cloacae. Report of a case cured by antibiotic therapy. Am J Dis Child 126: 352-353, 1973. 15. Iannini PB, Hull SF, Quintiliani R. Severe sepsis from Enterobacter. Arch Surg 107: 854-856, 1973. 16. Banks T. Fletcher R, Ali N. Infective endocarditis in heroin addicts. Am J Med 55: 444-451. 1973. 17. Menda KB, Gorbach SL. Favorable experience with bacterial endocarditis in heroin addicts. Ann Intern Med 78: 25-32, 1973. 18. Simberkoff MS, Isom W, Smithvas T, Noriega ER, Rahal JJ Jr. Two-stage tricuspid valve replacement for mixed bacterial endocarditis. Arch Intern Med 133: 212-216, 1974. 19. Magilligan DJ Jr, Quinn EL, Davila JC. Bacteremia, endocarditis, and the Hancock valve. Ann Thorac Surg 24: 508-518, 1977. 20. Bortolotti U, Thiene G, Milano A, Panizzon G, Valente M, Gallucci V. Pathological study of infective endocarditis on Hancock porcine bioprostheses. J Thorac Cardiovasc Surg 81: 934-942, 1981. 21. Levison ME. Therapy of endocarditis due to gram-negative bacteria and fungi. In: Sande MA. Kaye D, Root RK, eds. Endocarditis. New York: Churchill Livingstone, 151-161, 1984. 22. Gould K , Ramirez-Ronda CH, Holmes RK. Sanford JP. Adherence of bacteria to heart valves in vitro. J Clin Invest 56: 131541370, 1975. 23. Everett ED, Hirschmann JV. Transient bacteremia and endocarditis prophylaxis. A review. Medicine 56: 61-77, 1977. 24. Reyes MP, El-Khatib MR, Brown WJ, Smith F, Lerner AM. Synergy between carbenicillin and an aminoglycoside (gentamicin or tobramycin) against Pseudomonas aeruginosa isolated from patients with endocarditis and sensitivity of isolates to normal human serum. J Infect Dis 140: 192-202, 1979. 25. Freedman LR, Valone J Jr. Experimental infective endocarditis. Prog Cardiovasc Dis 22: 169-180. 1979. 26. Geraci JE, Wilson WR. Endocarditis due to gram-negative bacteria. Report of 56 cases. Mayo Clin Proc 57: 145-148, 1982. 27, Schneider PJ, Nernoff J. Gold JA. Acute salmonella endocarditis. Report of a case and review. Arch Intern Med 120: 478-482, 1%7. 28 Carruthers MM. Endocarditis due to enteric bacilli other than Salmonellae: case reports and literature review. Am J Med Sci 273: 20S211, 1977. 29. Reyes MP, Palutke WA, Wylin RF, Lerner AM. Pseudomonas endocarditis in the Detroit Medical Center. Medicine 52: 173-194, 1973. 30 Weiland M, Lederman MM, Kline-King C , Keys TF, Lerner PI, Bass SN, Chmielewski R, Banks VD, Ellner JJ. Left-sided endocarditis due to Pseudomonas aeruginosa. A report of 10 cases and review of the literature. Medicine 65: 180-189, 1986. 31 Ristuccia PA, Cunha BA. Enterobacter. Infect Control 6: 124-128, 1985. 32 Finland M, Barnes MW. Changing etiology of bacterial endocarditis in the antibacterial era. Experiences at Boston City Hospital 1933-1%5. Ann Intern Med 72: 341-348, 1970. 33 Sande MA, Scheld WM. Combination antibiotic therapy of bacterial endocarditis. Ann Intern Med 92: 390-395, 1980. 34 Tunkel AR, Scheld WM. Application of therapy in animal models to bacterial infection in human disease. Infect Dis Clin North Am 3: 441459, 1989. 35 Archer G , Fekety FR Jr. Experimental endocarditis due to Pseudomonas aeruginosa. 11. Therapy with carbenicillin and gentamicin. J Infect Dis 136: 327-335, 1977. 36 Reyes MP, Brown WJ, Lerner AM. Treatment of patients with Pseudomonas endocarditis with high dose aminoglycoside and carbenicillin therapy. Medicine 57: 57-67, 1978.
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37. Bryan CS, Marney SR,Alford RH, Bryant RE. Gram-negative bacillary endocarditis: interpretation of the serum bactericidal test. Am J Med 58: 209-215, 1975, 38. Toala P, Lee YH, Wilcox C, Finland M. Susceptibility of Enterobacter aerogenes and Enterobacter cloacae to 19 antimicrobial agents in vitro. Am J Med Sci 260: 41-54, 1970. 39. Sanders CC, Sanders WE Jr. Microbial resistance to newer generation p-lactam antibiotics: clinical and laboratory implications. J Infect Dis 151: 399-406, 1985. 40. Olson B, Weinstein RA, Nathan C, Kabins SA. Broad-spectrum @-lactamresistance in Enterobacter: emergence during treatment and mechanisms of resistance. J Antimicrob Chemother 11: 299-310, 1983. 41. Quinn JP, DiVincenzo CA, Foster J. Emergence of resistance to ceftazidime during therapy for Enterobacter cloacae infections. J Infect Dis 155: 942-947, 1987. 42. Spratt BG, Jobanputra V, Zimmermann W. Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escheiichia coli K-12. Antimicrob Agents Chemother 12: 406-409, 1977. 43. Tomasz A. From penicillin-binding proteins to lysis and death of bacteria: a 1979 review. Rev Infect Dis 1: 434-467, 1979. 44. Yoshimura F, Nikaido H. Diffusion of p-lactam antibiotics through the porin channels of Escherichia coli K-12. Antimicrob Agents Chemother 27: 84-92, 1985. 45. Boscia JA, Kobasa WD, Kaye D. Comparison of difloxacin, enoxacin, and cefoperazone for treatment of experimental Enterobacter aerogenes endocarditis. Antimicrob Agents Chemother 31: 458460, 1987.
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CASE REPORT
Enterobacter Endocarditis ALLAN R. TUNKEL', MICHAEL J . FISCH', ANDREW SCHLEIN2 and w . MICHAEL SCHELD~
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From the Division of lnfectious Diseases and Department of Internal Medicine, 'Medical College of Pennsylvania, Philadelphia, Pennsylvania, and >University of Virginia School of Medicine, Charlottesville, Virginia, USA Endocarditis due to Enterobacter species is very rare. We recently cared for a patient who developed E. cloacae endocarditis following mitral valve replacement with a porcine heterograft, and was successfully treated with antibiotic therapy alone. A review of the literature disclosed an additional 17 well-described cases of enterobacter endocarditis. Two-thirds of the patients had underlying cardiac disease. The mitral valve was most frequently involved (10116 cases) with 4 of the patients having concomitant aortic valve involvement. The overall mortality rate was 44.4%. Antibiotic therapy of enterobacter endocarditis should consist of the combination of a beta-lactam antibiotic and an aminoglycoside with careful monitoring of blood cultures to assure the adequacy of therapy. Resistance of enterobacter to previously susceptible antibiotics may occur during therapy due to induction of a chromosomallymediated beta-lactamase, necessitating a change in antimicrobial therapy. Valvular surgery is indicated for patients failing medical management. A . R. Tunkel, MD, PhD, Division of Infectious Diseases, Medical College of Pennsylvania, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129, USA
INTRODUCTION Endocarditis due to Gram-negative bacilli is unusual despite the high incidence of Gramnegative bacteremia associated with manipulation and infection of the genitourinary and intestinal tracts. Of 452 valvular infections reported in the 1960s, only 1.7% were caused by Gram-negative organisms (1) versus 7% in more recent series (2). The incidence of Gramnegative endocarditis is higher in prosthetic valve endocarditis, accounting for about 20% of cases of early and 10-14% of cases of late prosthetic valve endocarditis (3-5). Increases in the incidence of Gram-negative endocarditis are due, in part, to the advent of antibiotics which select out for resistant Gram-negative organisms, immunosuppressive therapy, cardiac valve replacement, and the increased frequency of intravenous drug abuse (2). Among the Gram-negative bacilli, endocarditis due to Enterobacter species is very rare. We recently cared for a patient with endocarditis due to Enterobacter cloacae following mitral valve replacement with a porcine heterograft. Here we discuss this case and review the literature on this entity. CASE REPORT The patient was a 57-year-old female with a long history of rheumatoid arthritis and chronic obstructive pulmonary disease who was diagnosed with non-Hodgkin's lymphoma 1.5 years prior to entry. She went into a complete remission following therapy with cyclophosphamide, etoposide, vincristine, S-fluorouracil. adriamycin, and dexamethasone. She did well until 1 week before admission when she presented
234 A . R. Tunkel el al.
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Table I. Clinical characteristics of patients with enterobacter endocarditis
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Case Age Sex no.
Valve involved
Underlying cardiac disease
Underlying conditions
Antibiotic therapy
Outcome
Ref. no.
Streptomycin, No sulfadiazine Penicillin, s t r e p N o tomycin
Survived Died
6
No
Died
8
Died
9
Died
10
Died
11
Survived
12
No
Died
13
No
Survived Survived
13
Died
15
1
28
M
Mitral
No
I.v. drug use
2
65
M
Aortic
?Rheumatic heart disease
3
22
F
Mitral
No
4
-
Tricuspid
5
-
Mitral
?Valve trauma secondary to pulmonary hypertension Prosthetic valve
Prostatic hypertrophy, transurethral resection of prostate, prostatic abscess Ureteral calcuPenicillin, streplus, cysto5copy tomycin, sulfadiazine, sulfawith meatomy thiazole, bacterioph age, polymyxin Pulmonary arteriosclerosis
6
48
M
Aortic. mitral
No
I.v. drug abuse
7
54
M
Aortic, mitral
Prosthetic valve
Urinary tract infection
-
Rheumatic heart disease Ventricular septa1 defect Congenital aortic stenosis, cornmissurotomy Rheumatic heart disease, mitral annuloplasty No I.v. drug abuse
8
3.5 M
9
8
F
-
10
13
F
Aortic
11
32
F
Aortic, mitral
12
52
M
Tricuspid
13
24
M
Tricuspid
14
30
M
15
28
M
Aortic, mitral Tricuspid
16
-
17
41
18
57
I.v. drug abuse, pulmonary embolus Rheumatic heart I.v. drug abuse disease I.v. drug abuse No
Mitral
Prosthetic valve (porcine)
M
Mitral
F
Mitral
Prosthetic valve (porcine) Prosthetic valve (porcine)
Rheumatoid arthritis, nonHodgkin’s lymphoma
Surgical therapy
Met hicillin, No chloramphenicol, erythromycin No Kanamycin, gentamicin, chloramphenicol ChloramphenNo icol, kanamycin, cephalothin
No Carbsnicillin. probenecid, kanamycin Chloramphenicol Yes
7
14
Chloramphenicol, streptomycin Nafcillin
No
Survived
16
No
Survived
16
Penicillin, streptomycin Oxacillin, cefanone, gentamicin Cephalothin, carbenicillin, gentamicin Tobramycin, gentamicin Ceftazidime, gentamicin
No
Survived Survived Survived
17
No
Died
20
No
Survived
Present case
Yes Yes
18 19
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Enlerobacter endocarditis 235
to an outside hospital with the acute onset of shortness of breath. Examination revealed that the patient was febrile to 38.8"C. markedly dyspneic, and was in congestive heart failure with a new mitrat regurgitation murmur. Myocardial infarction was ruled out by normal cardiac enzymes. One of 4 blood cultures grew Staphylococcus aureus and she was treated with intravenous (i-v.)nafcillin. However, the patient became hemodynamically unstable and was transferred to the University of Virginia Health Sciences Center where a cardiac catheterization revealed 4+ mitral regurgitation, a mild reduction in left ventricular function, and normal coronary artery anatomy. The patient underwent mitral valve replacement with a 25 mm-Hancock porcine valve prosthesis. Pathologic examination of the native valve revealed multiple chordae tendonae ruptures and a myxamatous mitral valve without evidence of endocarditis. Nafcillin was discontinued after a 14-day course. Her postoperative course was complicated by prolonged intubation, congestive heart failure, bronchospasm, and upper gastrointestinal hemorrhage. One week after the nafcillin was discontinued, the patient developed a cellulitis on the right forearm and intravenous cefazolin was begun. Over the next several days she began to improve, was extubated, and remained hemodynamically stable. Cardiac examination was normal without evidence of murmurs. Five days later, the patient spiked at temperature to 39.6"C accompanied by shaking chills. The pulse was 120 beatshin. respiratory rate 24/min, and blood pressure llOn0 mmHg. Examination revealed a few bibasilar crackles and a new grade III/VI holosystolic murmur best heard at the apex and radiating to the axilla. Four of 4 blood cultures obtained over a time period of 48 h grew Enterobacter cloacae and a central line catheter tip yielded 50 colony-forming units of the same microorganism. The minimal inhibitory concentration for ceftazidime was 1 mg/l. gentamicin 1 mg/l. piperacillin 16 mg/l and imipenem > 16 mg/l. Ceftazidime (2 g i.v. every 8 h) and gentamicin (50 mg i.v. every 24 h) were begun. Cardiac echocardiography showed a normal valve prosthesis with trace mitral regurgitation. Cardiac catheterization revealed a normal functioning prosthesis with a 1+ periprosthetic leak. It was felt that she would not be a good surgical candidate. The patient'scondition stabilized on antibiotic therapy. The trough serum bactericidal titer, measured by the guidelines of the National Committee for Clinical Laboratory Standards, was 1:256. Antimicrobial therapy was continued for 6 weeks. She remained afebrile without evidence of cardiac decompensation. Blood cultures remained negative 2 months after discontinuation of antibiotics. The patient was subsequently lost to follow-up.
MATERIALS A N D METHODS Cases of enterobacter endocarditis reported in the literature were identified using Index Medicus and by a literature search of the MEDLINE data base of the MEDLARS service, National Library of Medicine. Only English language articles were included. The references of these citations were reviewed in depth for additional cases. Reports that did not have in-depth case histories were not included in this review. To be part of this series, cases were required to contain information regarding cardiac valve involved, underlying conditions, medical and/or surgical therapy, and outcome. There were 17 well-described cases of enterobacter endocarditis in the literature from 1949 to 1990 (6-20). With the addition of our case, 18 cases were available for analysis (Table I). Some additional cases are alluded to in larger series, and some of the characteristics of these cases are described in the discussion.
RESULTS Enterobacter endocarditis occurred in 10 men and 5 women (gender not indicated in 3 cases). The average age was 33.7 years with a range of 3.545 years. The majority of the patients had mitral valve involvement (10 cases), including 4 cases with combined mitral and aortic valve involvement. All of the 5 cases of prosthetic valve involvement due to enterobacter occurred on prosthetic mitral valves. The majority of the patients (12/18) had underlying cardiac disease including the presence of prosthetic valves (5 cases), rheumatic heart disease (4 cases), valve trauma secondary to pulmonary hypertension (1 case), ventricular septa1 defect (1 case), and congenital aortic stenosis (1 case). Intravenous drug abuse accounted for 3 of the 4 cases of tricuspid valve endocarditis, 1 case on the mitral valve, and 2 cases of combined mitral and aortic valve endocarditis. The most common non-cardiac underlying condition was i.v. drug abuse (6 cases). Besides an enterobacter, other organisms were recovered in 2 cases. In patient 5, there
236 A . R. Tunkel et al.
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was concomitant endocarditis with S. aureus, Candida albicans, and Paracolobactrum aerogenes; in patient 14 with Enterococcus faecalis and the viridans streptococcus. Patients received a variety of antimicrobial agents with most regimens containing an aminoglycoside (Table I). Surgical therapy was performed in 3 cases with 2 of the patients surviving. The overall mortality rate was 44.4%, and was lower for right-sided (25%) as compared to left-sided (50%) enterobacter endocarditis in this series.
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DISCUSSION Many different bacterial organisms have been implicated in the causation of infective endocarditis. Streptococci and staphylococci account for 80-90% of cases. Although Gramnegative bacilli have been reported in a lower percentage of cases, it has become clear that the incidence of infective endocarditis due to these organisms has increased in recent years; 1.7% in the 1960’s (1) versus 7% in more recent series (2). Several explanations have been proposed to account for the lower incidence of Gram-negative, as opposed to Grampositive, endocarditis (2,21). These include the greater capacity of Gram-positive organisms (e.g. S. aureus) to adhere to valve leaflets (22), the lower frequency that Gram-negative bacteria are involved in transient bacteremias in healthy people (23), and that nonbacteremic isolates of Gram-negative bacteria are less resistant to serum bactericidal activity than Gram-positive organisms (24). In addition, Gram-negative bacteria are less able than Gram-positive cocci to induce endocarditis in an experimental rabbit model (25). In a review from the Mayo Clinic during the period 1958-1975, 56 cases of endocarditis due to Gram-negative bacilli were observed, most due to “fastidious” non-enteric organisms (26). The increased incidence of these organisms in infective endocarditis is due, in part, to the use of invasive diagnostic techniques, treatment with antibiotics, presence of cardiac prostheses, i,v. drug abuse, and improvement in microbiologic techniques (2). Gramnegative bacilli have accounted for about 20% of isolates in early and 1&14% of isolates in late prosthetic valve endocarditis (3-5). Among the Enterobacteriaceae, Salmonella species have accounted for the majority of isolates in early reports due to the affinity of these organisms for abnormal heart valves (27). In a review of 44 cases of endocarditis due to enteric Gram-negative bacilli other than salmonella (28), organisms identified were Escherichia coli (17 cases) Klebsiella-Enterobacter group (9 cases), Serratia marcescens (13 cases), Proteus and Providentia species (2 cases each), and Citrobacter (1 case). A recent increase in the frequency of endocarditis due to Pseudomonas aeruginosa has been observed, predominantly among patients who abuse i.v. drugs (29, 30). Enterobacter is a rare isolate in cases of Gram-negative endocarditis, accounting for only 6% of isolates in narcotic addict-associated Gram-negative endocarditis in one series (2). In our literature review, we could identify only 17 well-described cases. This low number may relate to the fact that the genus enterobacter was not defined as a separate entity until the 1960’s (31). Before then, the differentiation of enterobacter from klebsiella was not routinely performed, which led to the reporting of many infections being caused by the klebsiella-enterobacter group; organisms with this description were excluded from our analysis. Therefore, our selection of cases is biased since only those cases reported in the literature were available for review, and those cases may or may not be representative of all episodes of enterobacter endocarditis. Among the clinical characteristics of the 18 cases of enterobacter endocarditis described here (Table I), several points can be made. There was a wide variation in the age of the patients (3.5-65 years) with a mean of 33.7 years. Males outnumbered females in a ratio of 2: 1. The mitral valve was most frequently involved (10/16 cases) with 4 of the patients having
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Enterobacter endocarditis 231
concomitant aortic valve involvement. The tricuspid valve was affected in 4 cases, 3 of which occurred in intravenous drug abusers. Two-thirds of the patients had underlying cardiac disease including the presence of prosthetic valves, rheumatic heart disease, pulmonary hypertension, ventricular septa1 defect, or congenital aortic stenosis. Surgical.therapy was used only in 3 patients, 2 of whom survived. The overall mortality rate in our series was 44.4%. However, these data may be flawed because our series represents only welldescribed cases of enterobacter endocarditis. In a review of the Boston City Hospital experience with bacterial endocarditis from 1933-1965, 20 cases of endocarditis due to enterobacter were identified, although detailed information on these cases was not available (32); all the patients died. When combined with our data, the overall mortality rate for enterobacter endocarditis was 73.7%. Case fatality rates are likely much lower today with the availability of more effective antimicrobial therapy against Enterobacter species as well as valve replacement surgery for cases refractory to medical therapy. Mortality rates were lower for right-sided (25%) as compared to left-sided (50%) enterobacter endocarditis in our series. One patient with right-sided endocarditis underwent surgery with a positive result, and 2 patients with left-sided endocarditis had valve replacement, 1 of whom survived. The optimal management of enterobacter endocarditis remains unclear. In this series it is difficult to make specific antibiotic recommendations for the treatment of enterobacter endocarditis because the choice of a particular antimicrobial agent did not correlate with outcome. Therapy of enteric aerobic Gram-negative bacillary endocarditis should be guided by in vitro susceptibility testing and bactericidal synergy studies (33). The experimental rabbit model of infective endocarditis has been utilized to emphasize many of the therapeutic principles in the treatment of endocarditis due to these organisms (34). For example, the combination of carbenicillin plus gentamicin was more effective than either alone in the rabbit model of P. aeruginosa endocarditis (35). Similar results have been observed in the therapy of pseudomonas endocarditis in intravenous drug abusers (29, 36). Therefore, therapy should consist of a beta-lactam agent in combination with an aminoglycoside to which the organism displays in vitro susceptibility. Despite problems with interpretation, the therapy of aerobic Gram-negative endocarditis should be tailored to achieve trough serum bactericidal titers of at least 1:8 (37). The duration of therapy is controversial, but is usually continued 4-6 weeks. Repeat blood cultures are essential to delineate response to therapy because patients who fail to respond bacteriologically to medical management are candidates for surgical therapy. In practice, cure rates are better in patients with right-sided than left-sided Gram-negative endocarditis (21). A recent review has suggested that patients with left-sided endocarditis due to P. aeruginosa have a better chance for cure when treated with early valve replacement and appropriate antibiotics than when treated with antibiotics alone (30). In vitro susceptibility testing reveals that virtually all enterobacter strains are resistant to penicillin, ampicillin, erythromycin, clindamycin, vancomycin, and the sulfonamides (31, 38). The first generation cephalosporins also have little or no anti-enterobacter activity. Drugs with a moderate degree of in vitro activity include the second generation cephalosporins. trimethoprim-sulfamethoxazole, and the antipseudomonal penicillins. The third generation cephalosporins, imipenem, the aminoglycosides, and the quinolones have the highest in vitro activity. However, with widespread use of newer beta-lactam antibiotics, enteric Gram-negative bacilli including enterobacter have acquired the ability to develop resistance to these drugs (39). Shortly after cefamandole became available, reports of the emergence of resistance of Enterobacter species to the drug during therapy began to appear due to the presence of an inducible, chromosomally mediated beta-lactamase capable of inactivating cefamandole (40). There was also simultaneous development of cross-resistance to many of
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238 A. R. Tunkel et ai.
Scand J Infect Dis 24
the other new beta-lactam antibiotics including cefuroxime, third generation cephalosporins, monobactams, and broad-spectrum penicillins (39). Beta-lactamase induction with cefoxitin has been shown to confer resistance to ceftazidime (41). Two mechanisms have been proposed to account for the development of resistance in enterobacter isolates (39). The first mechanism, which produces multiple beta-lactam resistance, is the induction of chromosomal beta-lactamases that mediate resistance to nonsubstrate drugs by the creation of a nonhydrolytic barrier that blocks access to target proteins in the cell. In contrast to the newer cephalosporins, the activity of an antibiotic such as imipenem is unaffected by this beta-lactamase because imipenem, unlike most other beta-lactam agents, acts on penicillinbinding protein 2 which is present in low quantities within the cell as compared with the other lethal binding proteins (42, 43), and penetrates rapidly across the bacterial outer membrane, a property presumably related to its compact molecular structure (44). The second mechanism, which produces beta-lactadaminoglycoside resistance, involves a change in outer membrane permeability mediated by altered porin proteins (39). Based on the above observations, clinical failure of antimicrobial therapy against enterobacter isolates that have good initial in vitro susceptibilities may represent the emergence of multidrugresistant organisms. In these clinical situations, imipenem is the antimicrobial agent of choice. The quinolones may also be effective, although there is no clinical experience with the use of these agents in enterobacter endocarditis. Difloxacin has been shown to be significantly more effective than cefoperazone in the rabbit model of E. aerogenes endocarditis (45), and further studies may establish the effectiveness of the quinolones in this infection. There was no evidence of the development of resistance during therapy in our literature review of enterobacter endocarditis. In summary, we have described a case of enterobacter endocarditis and reviewed an additional 17 well-documented cases. Therapy of this infection should consist of the combination of a beta-lactam antibiotic and an aminoglycoside to which the organism displays good in vitro susceptibility with careful monitoring of blood cultures to assure the adequacy of therapy. Resistance of enterobacter to previously susceptible antibiotics may occur during therapy necessitating a change in antimicrobial therapy. Valvylar surgery is indicated for patients failing medical management. Further descriptions of cases of enterobacter endocarditis may aid in determining the optimal medical and surgical treatment of these patients.
ACKNOWLEDGMENTS We gratefully acknowledge Ms Mona Bernhardt and Ms Eve Lorraine Schwartz for secretarial assistance. This work was supported in part by a research grant (ROl-AI17904) and a training grant (T32-AI07046) from the National Institute of Allergy and Infectious Diseases. W. Michael Scheld is an established investigator of the American Heart Association.
REFERENCES 1. Pelletier LL, Petersdorf RG. Infective endocarditis: a review of 125 cases from the University of
Washington Hospitals, 1963-1972. Medicine 56: 287-313, 1977. 2. Cohen PS, Maguire JH, Weinstein L. Infective endocarditis caused by gram-negative bacteria: a review of the literature, 1945-1977. Prog Cardiovasc Dis 22: 205-242, 1980. 3. Watanakunakorn C. Prosthetic valve infective endocarditis. Prog Cardiovasc Dis 22: 181-192,1979, 4. Wilson WR, Danielson CK, Giuliana ER, Geraci 3E. Prosthetic valve endocarditis. Mayo Clin Proc 57: 155-161, 1982. 5. Karchmer AW. Treatment of prosthetic valve endocarditis. In: Sande MA, Kaye D, Root RK, eds. Endocarditis. New York: Churchill Livingstone, 165182, 1984. 6. Luttgens WF, Endocarditis in “main line” opium addicts. Arch Intern Med 83: 6 5 M 6 4 , 1949.
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Scand J Infect Dis 24
Enterobacter endocarditis 239
7. Sussman LN, Cohen I, Freund AJ. Acute Aerobacter aerogenes endocarditis complicating genitourinary tract infection. NY State J Med 50: 583-586, 1950. 8. Wallace CS. Bacterial endocarditis with emphasis on the Escherichia-Aerobacter group as the causative agent: report of a fatal case. Ann Intern Med 34: 1463-1472, 1951. 9. Bashour FA, Winchell CP. Right-sided bacterial endocarditis. Am J Med Sci 240: 411416, 1960. 10. Stein PD, Harken DE, Dexter L. The nature and prevention of prosthetic valve endocarditis. Am Heart J 71: 393407, 1966. 11. Ramsey RG, Gunnar RM, Tobin JR Jr. Endocarditis in the drug addict. Am J Cardiol25: 608-618. 1970. 12. Yeh TJ, Anabtawi IN, Cornett VE, White A, Stern WH, Ellison RG. Bacterial endocarditis following open-heart surgery. Ann Thorac Surg 3: 2 9 3 6 , 1967. 13. Caldwell RL, Hurwitz RA, Girod DA. Subacute bacterial endocarditis in children. Am J Dis Child 122: 312-315, 1971. 14. Lere RJ. Postoperative endocarditis due to Enterobacter cloacae. Report of a case cured by antibiotic therapy. Am J Dis Child 126: 352-353, 1973. 15. Iannini PB, Hull SF, Quintiliani R. Severe sepsis from Enterobacter. Arch Surg 107: 854-856, 1973. 16. Banks T. Fletcher R, Ali N. Infective endocarditis in heroin addicts. Am J Med 55: 444-451. 1973. 17. Menda KB, Gorbach SL. Favorable experience with bacterial endocarditis in heroin addicts. Ann Intern Med 78: 25-32, 1973. 18. Simberkoff MS, Isom W, Smithvas T, Noriega ER, Rahal JJ Jr. Two-stage tricuspid valve replacement for mixed bacterial endocarditis. Arch Intern Med 133: 212-216, 1974. 19. Magilligan DJ Jr, Quinn EL, Davila JC. Bacteremia, endocarditis, and the Hancock valve. Ann Thorac Surg 24: 508-518, 1977. 20. Bortolotti U, Thiene G, Milano A, Panizzon G, Valente M, Gallucci V. Pathological study of infective endocarditis on Hancock porcine bioprostheses. J Thorac Cardiovasc Surg 81: 934-942, 1981. 21. Levison ME. Therapy of endocarditis due to gram-negative bacteria and fungi. In: Sande MA. Kaye D, Root RK, eds. Endocarditis. New York: Churchill Livingstone, 151-161, 1984. 22. Gould K , Ramirez-Ronda CH, Holmes RK. Sanford JP. Adherence of bacteria to heart valves in vitro. J Clin Invest 56: 131541370, 1975. 23. Everett ED, Hirschmann JV. Transient bacteremia and endocarditis prophylaxis. A review. Medicine 56: 61-77, 1977. 24. Reyes MP, El-Khatib MR, Brown WJ, Smith F, Lerner AM. Synergy between carbenicillin and an aminoglycoside (gentamicin or tobramycin) against Pseudomonas aeruginosa isolated from patients with endocarditis and sensitivity of isolates to normal human serum. J Infect Dis 140: 192-202, 1979. 25. Freedman LR, Valone J Jr. Experimental infective endocarditis. Prog Cardiovasc Dis 22: 169-180. 1979. 26. Geraci JE, Wilson WR. Endocarditis due to gram-negative bacteria. Report of 56 cases. Mayo Clin Proc 57: 145-148, 1982. 27, Schneider PJ, Nernoff J. Gold JA. Acute salmonella endocarditis. Report of a case and review. Arch Intern Med 120: 478-482, 1%7. 28 Carruthers MM. Endocarditis due to enteric bacilli other than Salmonellae: case reports and literature review. Am J Med Sci 273: 20S211, 1977. 29. Reyes MP, Palutke WA, Wylin RF, Lerner AM. Pseudomonas endocarditis in the Detroit Medical Center. Medicine 52: 173-194, 1973. 30 Weiland M, Lederman MM, Kline-King C , Keys TF, Lerner PI, Bass SN, Chmielewski R, Banks VD, Ellner JJ. Left-sided endocarditis due to Pseudomonas aeruginosa. A report of 10 cases and review of the literature. Medicine 65: 180-189, 1986. 31 Ristuccia PA, Cunha BA. Enterobacter. Infect Control 6: 124-128, 1985. 32 Finland M, Barnes MW. Changing etiology of bacterial endocarditis in the antibacterial era. Experiences at Boston City Hospital 1933-1%5. Ann Intern Med 72: 341-348, 1970. 33 Sande MA, Scheld WM. Combination antibiotic therapy of bacterial endocarditis. Ann Intern Med 92: 390-395, 1980. 34 Tunkel AR, Scheld WM. Application of therapy in animal models to bacterial infection in human disease. Infect Dis Clin North Am 3: 441459, 1989. 35 Archer G , Fekety FR Jr. Experimental endocarditis due to Pseudomonas aeruginosa. 11. Therapy with carbenicillin and gentamicin. J Infect Dis 136: 327-335, 1977. 36 Reyes MP, Brown WJ, Lerner AM. Treatment of patients with Pseudomonas endocarditis with high dose aminoglycoside and carbenicillin therapy. Medicine 57: 57-67, 1978.
Scand J Infect Dis Downloaded from informahealthcare.com by University of Sydney on 01/03/15 For personal use only.
240 A .
R. Tunkel et al.
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37. Bryan CS, Marney SR,Alford RH, Bryant RE. Gram-negative bacillary endocarditis: interpretation of the serum bactericidal test. Am J Med 58: 209-215, 1975, 38. Toala P, Lee YH, Wilcox C, Finland M. Susceptibility of Enterobacter aerogenes and Enterobacter cloacae to 19 antimicrobial agents in vitro. Am J Med Sci 260: 41-54, 1970. 39. Sanders CC, Sanders WE Jr. Microbial resistance to newer generation p-lactam antibiotics: clinical and laboratory implications. J Infect Dis 151: 399-406, 1985. 40. Olson B, Weinstein RA, Nathan C, Kabins SA. Broad-spectrum @-lactamresistance in Enterobacter: emergence during treatment and mechanisms of resistance. J Antimicrob Chemother 11: 299-310, 1983. 41. Quinn JP, DiVincenzo CA, Foster J. Emergence of resistance to ceftazidime during therapy for Enterobacter cloacae infections. J Infect Dis 155: 942-947, 1987. 42. Spratt BG, Jobanputra V, Zimmermann W. Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escheiichia coli K-12. Antimicrob Agents Chemother 12: 406-409, 1977. 43. Tomasz A. From penicillin-binding proteins to lysis and death of bacteria: a 1979 review. Rev Infect Dis 1: 434-467, 1979. 44. Yoshimura F, Nikaido H. Diffusion of p-lactam antibiotics through the porin channels of Escherichia coli K-12. Antimicrob Agents Chemother 27: 84-92, 1985. 45. Boscia JA, Kobasa WD, Kaye D. Comparison of difloxacin, enoxacin, and cefoperazone for treatment of experimental Enterobacter aerogenes endocarditis. Antimicrob Agents Chemother 31: 458460, 1987.
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