Asian Cardiovasc Thorac Ann 2004;12:316-319
© 2004 Asia Publishing EXchange Ltd
Surgery for Active, Culture Negative Endocarditis
Makiko I Hasegawa, PhD,
Shunei Kyo, MD,
Haruhiko Asano, MD,
Kazuhito Imanaka, MD
Department of Cardiovascular Surgery, Saitama Medical School, Saitama, Japan
For reprint information contact: Kazuhito Imanaka, MD Tel: 81 492 761 562 Fax: 81 492 762 062 Email: imanaka{at}saitama-med.ac.jp Department of Cardiovascular Surgery, Saitama Medical School, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
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ABSTRACT
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Culture negative infective endocarditis (CNE) poses very difficult problems during treatment. In this study it was found that of 132 surgically treated patients with infective endocarditis, causative organism was not identified in 46 (34.8 %). Pre- and perioperative conditions and clinical results of these patients were evaluated. CNE remained very frequent even in these years, and it did not decrease with time. Antibiotic treatment prior to microbiological examinations was commonly observed (nearly 90% orally, and 70% intravenously). In average, it took more than 2 months to establish the diagnosis of CNE after the onset, and both aortic and mitral valves were affected frequently (19.0 %). New York Heart Association functional class IV was observed significantly more commonly (61.9%) than culture positive patients. Frequencies of prosthetic valve endocarditis (12.2%), periannular abscess (36.3%), and embolism (21.4%) were similar. Infection was fairly controllable before surgery in 43.9% of CNE patients and in-hospital mortality rate was 14.3%, both of which were comparable to those of all culture positive patients. However, recurrence rate was relatively higher (10.0%). The conditions and outcomes of CNE were comparable to Staphylococcal endocarditis in some aspects, and were relatively worse than overall culture positive endocarditis.
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INTRODUCTION
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Infective endocarditis (IE) is a formidable entity even nowadays. During treatment of IE, identifying the causative organism and administering effective antibiotics are very important. However, we sometimes encounter patients without positive culture result. In such cases, antibiotics in use may not be appropriate and special caution is required. In the present study, clinical conditions and results of surgically treated patients with culture negative endocarditis (CNE) were investigated.
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PATIENTS AND METHODS
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From January 1983 until December 2002, 132 patients (91 males and 41 females, mean age 50.8 years) underwent surgery for active IE at Saitama Medical School. Medically managed patients were not included in this study. IE was judged as "active" according to the criteria by Manhas.1 CNE was diagnosed when all blood and tissue culture specimens were negative for any microorganisms. According to this definition, the number of the causative organisms were undetermined (=CNE) 46 (34.8%), 
-Streptococci 40 (30.3%), Staphylococci 24 (18.9%), and miscellaneous 22 (16.6%). Culture specimens were obtained more than 3 times in all but one CNE patients, and twice in one patient. In 2 of 46 CNE patients, microorganisms were observed in histological specimen but culture results were negative (Grampositivecoccus1,Grampositiverod1).Theactivityof infection was classified into the following two stages.
Relatively controlled stage: High fever (>37.5°C) disappeared, and mild elevation of the leukocyte count (9000~12000/µL) or the serum CRP level (1.5~5 mg•dL–1) persisted. Or tissue specimen was positive for microorganism although fever subsided and the data were almost normal (3 patients). Uncontrolled stage: High fever with marked elevation of the leukocyte count (>12000/µL) and/or the serum CRP level (>5 mg•dL–1) persisted.
Periannular abscess was diagnosed only when infectious cavity was clearly formed around the annulus. Recurrent IE was excluded from prosthetic valve endocarditis. Surgery was carried out through a midline sternotomy and by using hypothermic cardiopulmonary bypass and cardioplegia. Affected tissues were radically resected, and prosthetic valve and/or prosthetic patch were sewn into place. Data of the continuous variables were expressed as Mean ± standard deviation. Student’s t-test or chi-square analysis were used to compare groups, and p < 0.05 was regarded as statistically significant.
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RESULTS
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Patient demographics and clinical results are shown in Table 1
. Age and gender were similar between CNE patients and culture positive IE patients.
1. ACTIVITY OF INFECTION
Surgery could be carried out at relatively controlled stage in 43.9% of the CNE patients. This frequency was significantly lower than -Streptococcal IE (p < 0.01), relatively higher than Staphylococcal IE, and was comparable to all culture positive IE (43.5%). Embolic events occurred in 21.4% of the CNE patients (cerebral 6, peripheral 3) before surgery.
2. CONDITION OF HEART FAILURE
New York Heart Association functional class (NYHA) was IV in 61.9 % of CNE patients. This was comparable with Staphylococcal IE, and was significantly more frequent than -Streptococcal IE (p < 0.01).
3. DURATIONS UNTIL DIAGNOSIS, REFERRAL, AND SURGERY
Diagnosis of IE was established more than 2 months after the onset in patients with CNE. Staphylococcal IE was diagnosed relatively earlier (p = 0.17) and Streptococcal IE was diagnosed later (p = 0.23) than CNE. Duration between diagnosis and referral to cardiovascular surgeons was relatively short in CNE patients, and duration between referral and operation was similar regardless of causative organisms.
4. AFFECTED SITES, PERIANNULAR ABSCESS, PROSTHETIC VALVE ENDOCARDITIS
Both the aortic and mitral valves were affected in 19.0 % of CNE patients and 8.4 % of all culture positive patients. This difference reached the statistical significance (p = 0.06). Periannular abscess was present in 36.3% of CNE patients. Prosthetic valve endocarditis comprised 12.8% of the CNE patients. On the other hand, among 22 patients with prosthetic valve endocarditis, Staphylococci were the most common organisms (31.8%) and CNE was the next.
5. OUTCOMES OF SURGERY
Mortality rate was 14.3% in CNE patients, which was significantly higher than a-Streptococcal IE (p < 0.01), relatively better than Staphylococcal IE, and was comparable to overall culture positive IE patients (14.1%). Durations of postoperative intensive care unit stay, hospital stay, the frequency of re-exploration for hemostasis and homologous blood transfusion were also similar to overall culture positive IE patients. Excluding immediate death cases, reoperation for recurrent IE was necessary in 8 patients. Recurrence rate of CNE was 10.0%, which was comparable to Staphylococcal IE and was relatively more frequent than in all culture positive IE (4.8%, p = 0.30).
6. CHANGE OF THE FREQUENCY OF CAUSATIVE ORGANISMS WITH TIME (FIGURE 1)
In our hospital, CNE was most frequent among surgically treated IE throughout the whole period. Evaluation of the frequency every 5 years revealed that CNE does not decrease with time and remains very common even in these years.
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Figure 1. Change of the frequency of causative organisms with time. Frequency of culture negative endocarditis did not decrease with time at all.
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7. PREMATURE ANTIBIOTIC TREATMENT
Before obtaining blood culture specimen(s), oral and intravenous antibiotics had been already administered in 84.4% and in 69.0% of CNE patients, and in 89.2 % and in 68.4% of all culture positive IE patients, respectively.
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DISCUSSION
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Identifying the causative organism of IE is very important, because the efficacy of antibiotic therapy depends on the sensitivity of the causative organism to the drugs used. However, it was unknown in more than one third of our patients. This was strikingly more frequent than reports especially from other countries.2–4 Obtaining serial blood culture specimens has been recommended in patients with possible IE,5 and previous use of antibiotics is a well-known reason for negative culture results.6,7 Of our patients’ cohort, however, premature use of antibiotics was very frequent even in these years. Some relationship between the high frequency of CNE and the high frequency of premature antibiotic therapy is strongly suggested. Fastidious organism is another possible reason for negative culture results.6 In patients with apparent CNE, serological tests should also be considered.2,8,9 As yet, however, we have no case that causative organism was identified by serological test.
Several difficult problems exist during treatment of CNE. The first problem is diagnosis. If blood culture is negative for microorganism, establishing the diagnosis of IE is very difficult until bacterial lesions are newly and/or clearly formed in the heart. On average, it took more than 2 months to make the diagnosis of CNE. Probably as a result, advanced NYHA class and involvement of both the aortic and mitral valves were observed more frequently in CNE patients than in culture positive patients.
The second problem is antibiotic therapy. Optimal choice of antibiotics in CNE patients is unknown. In this study, infection was uncontrollable before surgery in nearly 60% of our CNE patients, and recurrence was more common (10%) among CNE.
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LIMITATION OF THE STUDY
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Only patients whose infection had been medically uncontrollable were included in this study. Therefore, our data may not truly represent those of CNE in general. Moreover, non-infective endocarditis might not be excluded completely.
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CONCLUSIONS
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The prevalence of CNE was very high and is not decreasing with time. Premature antibiotic treatment was very common. It took rather long time to diagnose CNE, and several unfavorable aspects were demonstrated. Although mortality rates were comparable with culture positive IE patients, recurrence was frequent among CNE patients.
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REFERENCES
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ABSTRACT
INTRODUCTION
