Bacterial endocarditis:A retrospectivestudy Dariush Mostaghim, D.D.S., M.S.,* a.nd H. Dean Millard, Ann Arbor, Mich. UNIVERSITY
OF MICHIGAN
SCHOOL
D.D.S., MS.,“”
OF DENTISTRY
A retrospective study was done on patients admitted to the University of Michigan Hospital from 1962 to 1972 with a diagnosis of bacterial endocarditis. The findings in the group studied indicate that Streptococcus viridam was the predominant causative organism, males were affected three times as often as females, erythromycin was effective against organisms of oral origin, dental procedures were not definitely established as responsible for the onset of the disease in any of the cases, and rheumatic heart disease and congenital heart disease were the predominant, but not the only, predisposing factors.
B
acterial endocarditis (B.E.) is a serious disease. Despite the amazing progress in modern medicine and the availability of curative antibiotics, the mortality rate of B.E. is quite high. This disease, if cured, may still have disabling sequelae. The average hospitalization period for treatment of B.E. is about 6 weeks, and extensive care and medication are required. Hence, even if the victim of the disease recovers and escapes its sequelae, he has suffered a great financial loss. Recent advances in medicine have lengthened the life-span of many patients susceptible to B.E., so the dentist is being confronted more and more wibh these patients seeking dental care on an outpatient basis. A negligent practitioner may turn a simple dental procedure into a life-threatening situation. That a patient should suffer or even die as the consequence of a simple dental procedure is a tragedy. The purpose of this study was to provide up-to-date information about B.E. useful to the dental profession. The objectives of this study were as follows: 1. To determine predisposing factors to B.E. and find their incidence in the group of patients studied. “Visiting Assistant Professor of Dentistry, Department of Oral Diagnosis and Radiology; Assistant Professor of Dentistry, Department of Oral Diagnosis and Oral Medicine, The lYationa1 University of Iran School of Dentistry, Tehran, Iran. **Professor and Chairman, Department of Oral Diagnosis and Radiology.
219
2. To evaluate predominant causative microorganisms for B.E. and to determine if any change in the causative agents has occurred during recent years. 3. To determine the role of oro-dental conditions and procedures as precipitating factors in B.E. 4. To evaluate the sensitivity of causative microorganisms to selected antibiotics used in the treatment of B.E. 5. To evaluate the mortality rate of B.E. REVIEW OF THE LITERATURE Definition
“Bacterial endocarditis (B.E.) is a microbial infection of the heart valves or of the endocardium in proximity to congenital or acquired cardiac defects.“l Since the infection is caused by a variety of microorganisms (bacterial, mycotic, rickettsial), some have used the term infective endocarditis in the literature.2-” The disease has been classified as subacute bacterial endocarditis (S.B.E.) and acute bacterial endocarditis (A.B.E.) . Subacute bacterial endocarditis generally begins insidiously, occurs on pre-existing heart disease, and is often caused by indigenous organisms with low pathogenicity. Acute bacterial endocarditis begins abruptly, often develops on normal endocardium, is caused by highly pathogenic organisms, pursues a rapid course, and is fulminant.lp 3 Predisposing
factors
Rheumatic heart disease (R.H.D.) is almost universally accepted as the most important and prevalent predisposing factor in S.B.E. This association has been reported with different incidences in various surveys. Dormer8 reported R.H.D. underlying 63 per cent of cases of B.E., Wilkinson’l reported 62 per cent and Finland and Barnes3G found R.H.D. in 46 per cent of B.E. cases. Millard and Tupper” found a relationship between R.H.D. and B.E. in 66 per cent of the cases they studied, and Hobson and Jensen I5 found an 80 per cent relationship in the cases they studied. Congenital heart disease is another established condition predisposing to B.E. and is reported underlying 13.5 to 28 per cent of cases of B.E. in different studies 8, 9, 11,15 A history of rheumatic fever without resultant heart disease has been found in about 2 per cent of S.B.E. cases.” Patients with prosthetic heart valves are very susceptible to B.E.l”, 13,I4316,Ii Arteriosclerotic heart disease is considered to be one of the conditions predisposing to B.E. It has been reported in 4 to 6.5 per cent of B.E. cases.*’ 9, I13In Infective endocarditis has been reported as one of the serious complications of narcotic addiction. Endocarditis in these patients is usually acute and fulminating and involves a normal heart. This infection most commonly affects the right side of the addict’s heart and almost invariably is found in heroin “mainliners” who give themselves multiple daily unsterile intravenous injections.4p I8 Staphylococcus aureus is the most commonly found organism, and Streptococcus
Bacterial
endocarditis
221
viridans is found rarely.3l 4pl8 All of these findings are indicative of the contamination of blood by skin sepsis due to unsterile methods of injection. Precipitating
factors
Any procedure capable of producing bacteremia has the potentiality of precipitating B.E. in a susceptible patient. A bacteremia can be produced by a wide range of different procedures and conditions, such as infections of the upper respiratory tract, orodental conditions and procedures, urinary and gastrointestinal tract infections and manipulations, parturition, abortion, burns, insect bites, surgery, and trauma.ll 3l O Recently the causal relationship between bacteremia and B.E. in abnormal endocardium has been confirmed by experiments on animal models.41-43 Mouth
and
B.E.
As early as the 1920’s suspicion arose about the relation between extraction of infected teeth and heart disease. Calvylg believed that extraction of infected teeth could cause a latent heart infection to flare up. RushtonzO in 1930, reported the production of bacteremia after tooth extraction and discussed the relationship between extraction and S.B.E; Okell and Elliott,21 in 1935, proved the occurrence of transient bacteremia following tooth extraction and found a direct relationship between the incidence of bacteremia, the severity of gingival lesions, and the amount of damage induced during surgery. They reported postextraction bacteremia in 34 per cent of healthy and 75 per cent of septic mouths. Streptococcus viri&n.s was the most common organism in their experiences. in 1939 HopkinP also found Streptococcus viridans to be the most common microorganism in the bloodstream after extraction of teeth. Since then a cause-and-effect relationship between B.E. and teeth has been questioned, and many investigations have been carried out to prove this relationship.23-z5f29The following dental procedures have been shown to produce bacteremia: exodontia,23s*Obrushing the teeth,23 chewing hard candy,23 gingivectomy, scaling and curettage,25t29 endodontic treatment with instrumentation forced beyond the apex,*Oand even ultrasonic scaling.*’ Beers,31using anaerobic and aerobic techniques found pre-extraction bacteremia in dental patients and also in healthy normal controls. In his study extraction caused an increase of the number of bacteria in the bloodstream. Additional support for the relationship between the mouth and B.E. is found in a review of the case histories in which B.E. occurred after dental procedures. Many researchers have found a history of dental procedures preceding B .E .3,5y7-gv***32p33 This association is very hard to prove, especially in cases of S.B.E. The incidence of this relationship has been found with different ratios in the literature. In 1950 Robinson and colleagues3* in a review of the literature, found dental procedures to be implicated in 10.8 per cent of all cases of B.E. Millard and TuppeP found preceding dental procedures in 26 per cent of patients with S.B.E. Croxson and co-workers33 reported this relationship in 40 per cent of patients with B.E. resulting from Xtr. viridans.
It is almost universally are
most
frequently
Oral
Burg.
August,
1975
agreed that B.E. in general and S.B.E. in particular
caused
by
Str.
viri&m~
7 . '2 3, G, 6, R, o, I13 In, 22, 33, 'W 3G Sk.
viridans as a normal inhabitant of the mouth and throat, is the most common microorganism isolated from this area,21 and it also has been found to be the most common microorganism in blood cultures following dental procedurcs.2”-2”~ 27-m Bahn and associates*” have been able to induce B.E. by introducing 8. and X. m&is into the wound socket of an extracted incisor, into the gingiva, or by intravenous injection into the marginal ear vein of the rabbit. The animals were predisposed to B.E. by sterile heart catheterization. The induced endocardial lesions were reported histologically similar to those observed in human B.E. Most recently McGowan and Hardie** produced B.E. in rabbits following dental manipulations after inducing sterile endocardial lesions. m8utans
Prophylactic
measures
for B.E. in dentistry
The first step in prophylaxis is the detection of patients susceptible to endocarditis, and this is carried out by careful history taking.‘* Before performing any dental procedure capable of producing transient bacteremia, the susceptible patients should be premeditated by an appropriate antibiotic regimen.l’ (i Myall and GregoryI believe that even a periodontal examination should be made under an antibiotic cover. Inasmuch as Streptococcus viri&,?as is considered to be the most common cause of B. E. with respect to oral origin, prophylaxis is directed against this organism” in dentistry. However, several other organisms with oral origin have proved to be responsible for B.E., namely, Staphylococci, Enterococci, Candida,? Str. faecalis, and even anaerobic gram-negative rods9 Axelrod and colleagues,12 in 1973, reported a well-documented case of B.E. caused by Lactobacillus 3 weeks after scaling in a previously healthy person. Importance
and mortality
Bacterial endocarditis is a serious disease and, if left untreated, is always fatal.‘9 Ii It has a high mortality rate, even with proper modern therapeutic measures.‘, 6 J)ormer,s in 1958, reported a mortality rate of 43 per cent in patients with B.E., considering early and late deaths. Millard and Tupper,s in 1960, reported a mortality rate of 20 per cent in their survey of patients with S.B.E. In 1971 Neutze and Arte? reported a 42 per cent death rate from B.E. in Green Lane Hospital in New Zealand. The mortality rate of B.E. in patients with valvular prosthesis is much higherI and has been reported up to 77 per cent.lO Financial
loss and sequela
The average hospitalization period for B.E. treatment is 4l to 6 weeks.G During this period, the patient is treated with very high doses of antibiotics, in most cases daily doses of 12 to 20 x 10Gunits of penicillin G and 1.0 Gm. of strept0mycin.l In some cases, even 48 x 10” units of daily penicillin have been used.12 In patients with prosthetic valves, a combination of different anti-
Volume 40 Number 2
Bacterial
I. Incidence 1962-1972
Table
endocarditis
of acute and subacute cases of B.E. studied
Condition
S.B.E. A.B.E. Undetermined B.E. Total
No.
of cases 51 9 4 s4
223
at U.M.H.,
Per cent
79.68 14.06 6.25 100
biotics is necessary.‘3 Considering the expenses necessary for hospitalization, medication, and professional care plus income loss during the course of the disease, the financial loss suffered by the patient is very high. Even if the victim survives, he may suffer from serious crippling sequela, such as hemiparesis, blindness, heart failure, and glomerulonephritis, which are the result of systemic emboli.lp Fl 8$*Is I4 METHOD
OF THE STUDY
Hospital records of patients with the diagnosis of B.E. at the University Hospital in Ann Arbor, Michigan (U.M.H.) for the lo-year period from 1962 to 1972 were selected through the use of computer punch cards. Only those cases that were well documented with the presence of positive blood or valve cultures or cases confirmed by postmortem examination were accepted for the study. Cases with inadequate data were excluded. The following data were collected for each case : 1. Age 2. Sex 3. Race 4. Probable precipitating factor 5. Clinical diagnosis 6. Predisposing factors 7. Dental treatment during hospitalization 8. Blood or valvular culture 9. Sensitivity tests 10. Treatment 11. Recurrence 12. Death 13. Postmortem examination The collected data were analyzed statistically, and some tests of significance were performed in necessary areas. RESULTS
Seventy-eight charts showing a diagnosis of B.E. were retrieved for the lo-year period from 1962 to 1972. During the same period of time, a total of 236,420 patients were admitted to the University Hospital. Thus the incidence of B.E. among other hospital admissions, on the basis of clinical diagnosis, was 0.0329 per cent.
224
Mostnghiw
a)td
Oral August,
Millwd
II. Underlying heart conditions 1T.JI.II. from 1962 to 19i:!
Table
in sixty
patients
with
X0. of patients
Condition
B.E. treatc>d at Per cent
R,.H.D. C.H.D. R.H.D. or C.H.D. undetermined Syphilitic heart disease Arteriosclerotic heart disease Normal
24 12 5 2 2 15
40 20 8.33 3.33 3.33 25
Total
E-l
100
Table
Age distribution
Ill.
Aoe
gro;ps
I
I /
I
II
I /
among B.E. patients III
Age range S.B.E. A.B.E. Undetermined B.E. Total B.E.
0 to 9 10 to 19 20 to 29 2 10 4 L 3
Per cent
10.93
1 7
7 ___ 10.93
- 13 20.31
I /
IV
I j
v
30 to 39 40 to 49 9 8 9 ___ 14.06
2 10 ___ 15.62
at U.M.H., I 1
VI
I 1
1962 to 1972 VII
I 1 VIII
50 to 59 60 to 69 70 to 79 7 4 4 1 I 1 9 14.62--
Surg. 1975
5
4
7.81
6.25
I j Total 51 9 4 64 100
Because of inadequate documentation, eighteen charts were excluded in the final analysis. Four well-documented recurrences occurring during the period of study were added to the sixty documented cases, making a total number of sixty-four cases. Classification
Table I shows the incidence Predisposing
of A.B.E.
versus S.B.E. in the cases studied.
factors
Table II shows the predisposing factors in sixty studied patients. To avoid repetition, the recurrences were not included in this analysis. As it is reflected in the table, R.H.D. was the most prevalent underlying condition and was detected in 40 per cent of the patients. C.H.D. proved to be the second major predisposing condition, with an incidence of 20 per cent, while syphilitic and arteriosclerotic heart disease were each detected in almost 3 per cent of the cases. Twenty-five per cent of the cases occurred on hearts with no previous history of an abnormal condition. The incidence of S.B.E. on normal hearts was 13.72 per cent, while six of nine cases of A.B.E. occurred on normal hearts. In one of the S.B.E. cases and two of the A.B.E. cases occurring on normal hearts the patients were heroin addicts and mainliners. Another patient was diabetic but had no detectable heart involvement. The age distribution is reflected in Table III.
Volume
40
Number
2
Table
Bacterial
IV. Sex distribution
among sixty
at U.M.H.,
No. of cases
Sex
Female Male
-M =
V. Sex distribution
1962-1972 23.33 76.66
60 1
F
225
Per cent
14 46
Total
Table
B.E. patients
endocarditis
100
3.28
among total admissions at U.M.H.
(last 3 years of
study) Sex
No.
Female Male
Per cent
36,935 32,055
Total F -=M
Table
of admissions
VI. Predisposing
53.5 46.5
68,990 1.15
100
1.0
factors to B.E. in females and males seen at U.M.H.,
1962-1972 Female
conclitios
No.
of cases )
R.H.D. C.H.D. R.H.D. or C.H.D. Prosthetic valve Syphilitic H.D. Arteriosclerotic H.D.
-
Total abnormal hearts No. of normal hearts
13 1
Total
ii-
cases
Pm cent
i
I 1 No.
Yale
of uxes (
Per
oewt
17 9 4 -
2 1
: 92.85 100
32 14 46
69.56 100
Sex distribution among B.E. patients studied and total admissions is reflected in Tables IV and V. In an attempt to find an explanation for the discrepancy in sex distribution, the detected organic heart diseases are tabulated in Table VI for each sex group. As it is reflected in the table, the incidence of organic heart diseases was even lower in male patients than in female patients. Addiction
Six of the B. E. patients studied were heroin addicts, all of them “mainliners.” In three cases, B.E. developed on normal hearts. In the remaining three patients B.E. developed over abnormal hearts (R.H.D., syphilitic heart disease, prosthetic valve).
2%
Mostaghim
Table
VII. Etiologic
Oral Surg. August, 1975
and Millard microorganisms
Organisms Streptococci viridans fecalis la&is enterococci liqueficience mitis E:% zymogenes uberus
of B. E., U.M.H.,
19621972 (10 years) No. of cases 19 4 3 2 2 1 1 1
& Y microaerophilic Total Staphylooocd aureus coagulate-negative coagulase-positive microaerophilic Total Miscellaneous Diphtheroids Can&da parapsilosis Cram-negative rods Pneumococci Haemoptilus in&enzae Haemophilus para in&enzae Paracolon Klebsiella Pseudomonas Proteus mirabilis
1 1 2 1 13
Total Total number of organisms
76
Eight organisms were cultured from the blood of these patients : Staphylococci, coagulase-positive Pseudomonas Staphylococcus aureus Str. faecalis Str. viridans Precipitating
3 2 1 1 1
oral factors
Only in nine cases (14.06 per cent) were oral conditions and dental procedures related to the onset of B.E. recorded on the patients’ charts.. They ranged from simple prophylaxis, orthodontic treatment, and tooth capping to root canal therapy, extraction, pericoronitis, and dental abscess. The following microorganisms were cultured from the blood of these patients : 3 Str. viridans 1 Str. l&is 1 Streptococcus, alpha hemolytic
Volume 40 Number 2
Bacterial
Staph. aurew Staphylococcus, microaerophilic Haemophilus para influenzae Klebsiella organisms The interval between dental procedure or infection symptoms ranged from a few days to 8 weeks. Causative
endocarditis
227
1 1 1 1 and the onset of B.E.
microorganisms
The microorganisms isolated from the blood and valve culture of the patients are reflected in Table VII. Seventy-six microorganisms had been isolated from sixty-four cases. Some cases showed multiple causal organisms. In the analysis and discussion, each separate organism is considered one case. Streptococcus viridans proved to be the most common microorganism in this study and accounted for 25 per cent of all the responsible organisms. Str. viridans comprised 37 per cent of the S.B.E. cases (nineteen out of fifty-one). Sensitivity
of microorganisms
to antibiotics
Not all the isolated organisms were subjected to sensitivity tests. All of those tested were not tested against the same combination of antibiotics. With a few exceptions, most of the organisms were tested against penicillin, erythromycin, tetracycline, and streptomycin. Therefore, analysis was performed on these four antibiotics. Although it has been stated that almost every microorganism that has been identified has been isolated at one time or another from the oral cavity,37 it seems reasonable to exclude the remote possibilities and base the analysis on the more probable factors. In this regard, the following organisms were excluded from the data analysis: 1 Paracolon Klebsiella 1 Pseudomonas 2 Proteus mirabilis 1 The above organisms are considered neither indigenous nor supplemental oral flora. Sensitivity
to penicillin
Penicillin-sensitivity tests were done in fifty-nine cases. Forty-one (69.49 per cent) of these organisms were penicillin sensitive. In fifty-five microorganisms of probable mouth origin, forty-one (74.54 per cent) were penicillin sensitive. All Streptococcus viridatzs organisms proved to be penicillin sensitive. The following organisms were either moderately sensitive or resistant to penicillin : Str. famedis 4 cases 1 Peptostreptococcus sp. 2 Staph. aureus
Oral Surg. August, 1975
3 Coagulase-positive staphylococcus 1 Coagulase-negative staphylococcus 1 Haemophillus influenzae 1 Gram-negative rods” 1 Candida’ In three resistant cases (pepto-str., Staph. aureus, coagulase-positive staphylococcus), the patients had been under antibiotic therapy prior to blood culture and sensitivity test, although the nature of the antibiotics was not mentioned in the charts. Sensitivity
to erythromycin
Sensitivity to erythromycin was evaluated in forty-four microorganisms with possible mouth origin. Forty-one (93.18 per cent) cases proved to be erythromycin sensitive. The following were resistant to erythromycin : 1 case Staph. aureus 1 Str. faecalis 1 Candida’ No Str. viridans orga,ni.snw resistant to erythromycin were recorded. Sensitivity
to tetracycline
Sensitivity tests to tetracycline were available on forty-six microorganisms with possible mouth origin. Thirty-six cases (78.20 per cent) were sensitive to tetracycline. The resistant organisms were : 1 case Staph. aureus 1 Coagulase-nqative staphylococcus 5 Str. faecalis 1 Alpha streptococcus 1 Str. viridans 1 Candida” Sensitivity
to streptomycin
Sensitivity tests to streptomycin were available on forty-four microorganisms with probable oral origin. Only twenty-one (47.72 per cent) were streptomycin sensitive. Among thirteen Str. viriclans cases, ten (76.92 per cent) were resistant to streptomycin. That is, only 23.08 per cent of Str. viridans organisms were sensitive to streptomycin. The resistant organisms were : Xtr. viridans 10 cases 5 Str. famecali.s 1 Alpha streptococcus 1 Microaerophilic streptococcus 1 Str. liqueficience 1 Peptostreptococcus sp. 1 Coagulase-positive staphylococcus 1 Coagulase-negative staphylococcus 1 Candida* *Natural
resistance.
Volume Number
40 2
Bacterial
endocarditis
229
Fisher’s exact test was used for statistical comparison between the sensitivity frequencies of penicillin and the other three antibiotics, each pair at a time. The difference between erythromycin and penicillin sensitivities is statistically significant (P = 0.012). The difference between the sensitivities to penicillin and streptomycin is also statistically significant (P = 0.0056). The sensitivity to penicillin was not statistically significantly less than tetracycline (P = 0.421). Mortality
rate
Twenty-one of sixty-four cases ultimately terminated fatally during the 10 years of study. The mortality rate among these patients was 32.8 per cent. There were nineteen cases of Str. ciridnns B.E. in this study. Four of them terminated fatally. Thus, the Str. wiridans mortality rate was 21.5 per cent. DISCUSSION Predisposing
factors
Forty per cent of the patients showed a history of R.H.D. Twenty per cent of the patients had underlying C.H.D. Although the incidence of these two heart diseases as factors predisposing to B.E. was slightly different from that reported in other studies, our findings were in agreement with others in that these were the most frequent heart abnormalities predisposing to B.E.8, g*I1336 Syphilitic and arteriosclerotic heart diseases were each recorded in the history of 3.33 per cent of the patients studied. In former studies the incidence of these two diseases in B.E. patients was reported as being from 4 to 6.5 per cent.8l sl llp l5 In this study, 13.72 per cent of the S.B.E. cases occurred on apparently normal hearts. In the present study, six of the nine A.B.E. cases occurred on normal hearts. This is in agreement with other studies. * In two of the A.B.E. cases on normal hearts, the patients were heroin mainliners. Age
distribution
The incidence of B.E. in some age groups differed not significant statistically (x2 = 7.25, D.F.7, P N 0.6).
slightly,
but this was
Sex distribution
Males were affected more than three times as often as females. This sex predilection was statistically significant when compared to the male : female ratio of total hospital admissions for the last 3 years of the study (x2 = 22, D.F.1, P < 0.001). The reason for this predilection cannot be easily explained. It does not seem to be correlated with the incidence of clinically detectable underlying heart abnormalities. Some unidentified environmental factors may be responsible for this tendency. As the males are subjected to more everyday stresses, stress may play a part in this regard. Angrist and associates3” have produced changes within the valvular tissues of rats under stress and concluded that these nonbacterial endocardial changes could predispose hearts to infection.
Ej-ythj-omyc3n
======P============================== ==============2===5=======-i====~====== ==1===============2======EP==--___-__
-------
93% 80.9%
Estolate !
Stearate Tetracycline
78.26%
================================= ==================-===========z ==I==r====I===========I=========~
88.0% I Penicillin
============================= ============================= =============================
74.52% 76.6%
i-I
I Streptomycin
1
5=================~ -----------__-----======3===1======== -
47.72% ^
L-A
==== ==== Present ==== Pig. 1. Sensitivity of microorganisms 1972) compared with Khairat’s study.3o
r^
Y.b%
Study in bacterial
lIRIIl Khairat’s endocarditis
patients
Study28 (U.M.H.,
196%
Addiction
Six of the patients under study were “heroin mainliners.” Three cases occurred on normal hearts. As the present sample is very small, statistical analysis does not seem to be appropriate Whether or not development of B.E. in addicts is merely due to repeated unsterile intravenous injections remains unanswered on the basis of these data. Precipitating
oral
factors
In only 74 per cent of the cases were oral pathosis and dental procedures assumed to he responsible for the development of B.E. Although the history suggested a close relationship between the oral conditions and the development of B.E. in these patients, judgment is very difficult on the basis of the present data. Although the oral procedures were the only suspicious factors recorded in the history of the patients, other possibilities cannot be ruled out. All but one of the organisms isolated in these pat.ients were among the normal flora of the mouth. The exception was Klebsiella, cultured in a patient with a heart prosthesis 12 days after multiple dental extractions. Although Klebsiella organisms arc not considered to be indigenous or supplemental oral flora, they have occasionally been reported in suppurative dental lesions’” and isolated from postextraction blood cultures.38 In 1960 Millard and Tuppe? reported the incidence of oral conditions as precipitating factors in 26 per cent of S.B.E. patients in this same hospital. Croxson and associates3” in 1971, found this incidence in 40 per cent of B.E. patients. The decrease in the incidence of S.B.E. from an oral source may be the result of improvement of oral health and/or better preventive measures.
Volume Number
40 2
Frequency
Bacterial endocarditis of causative
23 1
microorganisms
Streptococci, especially Str. viridans, proved to be the most frequent causative organisms in this study. This finding is in agreement with all other previous studies.1, 3, 5, 6, 8, 9, 1% 15, 2‘4 33, 34, 36 2%. uiridans was responsible in 25 per cent of BE. and 37 per cent of S.B.E. cases in the present study. Millard and TuppeP reported the incidence of Str. viridans in 64 per cent of S.B.E. cases in this same hospital. The lower incidence of Str. virtians S.B.E. and also the decrease in the incidence of dentally inflicted S.B.E. cases in this study together are strongly suggestive of improvement of oral hygiene and preventive measures. Inasmuch as only nine of the organisms were gram negative, and only four of these may be found in oral flora, and just one was a fungus organism, antibiotics effective against gram-positive organisms may still be considered reliable for B.E. prophylaxis in most dental patients. Sensitivity
In this study, the effects of four currently used antibiotics were evaluated against the isolated microorganisms in vitro. Erythromycin proved to be the most effective agent. Erythromycin was even significantly more effective than penicillin, the universally recommended antibiotic,lv 6 for B.E. prophylaxis in dental procedures. The effect of penicillin and tetracycline did not differ significantly in this study. Streptomycin proved to be the poorest antibacterial agent against the microorganisms cultured within this study. None of the Str. virida,ns organisms was resistant to erythromycin or penicillin. Only one Str. viriclmns strain was resistant to tetracycline, while 77 per cent of the Str. viridans organisms proved to be resistant to streptomycin. Khairat,28 in 1966, evaluated the sensitivity of postextraction blood organisms to twenty-two different antibacterial agents in vitro. He also found erythromycin the most effective of the currently used antibacterial agents. Although the present study and that of Khairat were performed on two completely different groups of pa.tients, the results are very similar. Fig. 1 shows a comparison between the results of these two studies. The close agreement between the two studies cannot be attributed to chance. Tetracycline is a broad-spectrum antibiotic and is effective against both gram-positive and gram-negative organisms, but as the incidence of gramnegative bacteria originating from the mouth is very low, as shown in the present study, there would be no advantage in using tetracycline for S.B.E. premeditation. Still the question remains whether these antibacterial agents are as effective in vivo as they proved to be in vitro. KhairaP compared the effect of intravenous tetracycline and oral tablets of erythromycin as prophylactic covers for
Oral Surg. August,
1975
dental extractions. He conclucicd that intravenous tetracycline was significantl! more effective than oral crythromycin. He attributed this finding to the mow readily available blood concentration through the use of intravenous administration of tetracycline. Considering the above discussion, more in vivo studies would be in order, especially as erythromycin is almost a harmless antibiotic with extremely low toxicity, particularly when used for a short period of time.40 SUMMARY AND CONCLUSIONS Records of the patients with the diagnosis of bacterial endocarditis (B.E.) at the University Hospital in Ann Arbor, Michigan, were drawn out for the IO-year period from 1962 to 1972. Sixty well-documented cases with four reliable recurrences were accepted for the study, and then the collected data were statistically analyzed. The purpose of the study was to evaluate the validity of the present trends in dental prophylaxis against B.E. Analysis of the collected data showed that: 1. B.E. affected males three times as often as females. 2. Rheumatic and congenital heart diseases were the predominant factors predisposing to B.E. 3. Streptococcus vbidn~s was the organism most frequently cultured from the blood of the affected patients. 4. Erythromycin was the most effective antibiotic against the organisms with possible oral origin, in vitro. 5. There was evidence that suggested some oral procedures and infections were responsible for the development of B.E. Conclusive proof of such a cause-and-effect relationship was impossible in this study. A longterm well-planned prospective study is suggested for more reliable conclusions. 6. “Mainlining” by drug addicts has emerged as an important precipitating cause of bacterial endocarditis. 7. The mortality rate among these patients was 32.8 per cent. 8. The mortality rate for B.E. due to Streptococcus viridam was 21.5 per cent. REFERENCES
1. Cluff, L. E., and Fekety, F. R,.: Bacterial Endocarditis. In Harrison’s Principles of Internal Medicine, ed. 6, New York, 1970, McGraw-Hill Book Company, Inc., Vol. 1, pp. 767-770. 2. Thayer, W. S.: Bacterial or Infective Endocarditis, Edinburgh Med. J. 38: 237-265, 307-334. 1931. 3. Lerner,’ Philip, and Weinstein, Louis: Infective Endocarditis in the Antibiotic Era, N. Engl. J. Med. 274: 199-206, 1966. 4. Cherubin, C. E., et al.: Infective Endocarditis in Narcotic Addicts, Ann. Intern. Med. 69: 1091-1098, 1968. 5. Salma!, Laurence, William, F. H., and Palladina, V. 5.: Fatal Bacterial Endocarditis Followmg Tooth Removal, ORAL SURG. 30: 749-754, 1970. 6. American Heart Association: Prevention of Bacterial Endocarditis, J. Am. Dent. Assoc. 85: 1377-1379, 1972. 7. Neutze, J. M., and Arter, W. 5.: Bacterial Endocarditis and the Dentist, N. Z. Dent. J. 67: 79-84, 1971.
Bacterial
endocarditis
233
8. Dormer, A. Eric: Bacterial Endocarditis; Survey of Patients Treated Between 1945 and 1956, Br. Med. J. 1: 63-69, 1958. 9. Millard, H. D., and Tupper, C. J.: Subacute Bacterial Endocarditis; a Clinical Survey, J. Oral Surg. 18: 224-229, 1960. 10. Shafer, R. B., and Hall, ‘Wendel: Bacterial Endocarditis Following Open Heart Surgery, Am. J. Cardiol. 25: 602-606, 1970. Il. Wilkinson, Matthew: Bacterial Endocarditis and Focal Infection, Dent. Pratt. 17: 201-204, 1967. 12. Axelrod, Judith, et al.: Endocarditis Caused by Lnctobncdlus plantnrum, Ann. Intern. Med. 78: 33-37. 1973. 13. Archard, H. O:, and Roberts, W. E.: Bacterial Endocarditis After Dental Procedures in Patients With Aortic Valve Prosthesis, J. Am. Dent. Assoc. 72: 648-652. 1966. 14. Myall, R. W., and Gregory, H. S.: Current Trends in Prevention of Bacterial Endocarditis in Susceptible Patients Receiving Dental Care, ORAL SURG. 28: 813-818, 1969. 15. Hobson. F. G.. and Jensen. B. E. J.: Teeth. Strentoooccus viridnns and Subacute Bacterial Endocarditis, br. Med. J. i: 1501-1505, 1956. A 16. Bottomley, W. K., Willis, P. W., and Fekety, F. R.: The Dental Patient With a Heart Valve Prosthesis; Preoperative and Postoperative Conditions, Mich. Dent. Assoc. J. 51: 149-151, 1969. 17. Tanenbaum, Considerations in Patients With Prosthetic Heart H. L.: Prophylactic Valves Undergoing Dental Procedures, Med. Ann. D. C. 41: 457-458, 1972. 18. Menoa, K. B., and Gorbach, S. L.: Favorable Experience With Bacterial Endocarditis in Heroin Addicts, Ann. Intern. Med. 78: 25-32, 1973. 19. Calvy, P. J.: Dental Surgery and Organic Heart Disease, J. A. M. A. 74: 1221, 1920. 20. Rushton. M. A.: Subacute Bacterial Endocarditis Followins Extraction of Teeth and Tonsils,‘Guy’s Hosp. Rep. 80: 39-44, 1930. 21. Okell,. C. C., and Elliott, S. D.: Bacteremia and Oral Sepsis; With Special Reference to Etiology of Subacute Endocarditis, Lancet 2: 869-872, 1935. 22. Hopkins, J. A.: Streptococcm wiridans Bacteremia Following Extraction of Teeth, J. Am. Dent. Assoc. 26: 2002. 1939. Bacteremia, ORAL Suao. 7: 609, 1954. 23. Cobe, H. M.: Transistory 24. Varaas, B., et al.: Effects of Certain Factors on Bacteremias Resulting From Gingival Resection, J. Periodontol. 30: 796-207, 1959. M. B., and Kobernick, 8. D.: Bacteremia After Prophylaxis, J. Am. Dent. 25. Winslow, Assoc. 61: 69, 1960. 26. Bender, I. B., et al.: Dental Procedures in Patients With Rheumatiic Heart Disease, ORAL SURG. 16: 466, 1963. and Hand 27. Bandt. C. L.. Korn. N. A.. and Schaffer. E. M.: Bacteremias From Ultrasonic Instru’mentation, J.‘Periodbntol. 35: 214,’ 1964. 28. Khairat, 0. : An Effective Antibiotic Cover for Prevention of Endocarditis Following Dental and Other Postouerative Bacteremias. J. Clin. Pathol. 19: 561-566. 1966. Foll&ing Periodontal Scaling ‘in Patients With 29. Conner, H. D., et al:: Bacteremia Healthy Appearing Gingiva, J. Periodontol. 38: 466-472, 1967. 30. Tamimi, H. A., Thomassen, P. R,., and Moser, E. H., Jr.: Baeteremia Study Using a Water Irrigation Device, J. Periodontol. 40: 424.426, 1969. 31. Beers, Royce L.: Reduction of Dental Extraction Bacteremias by Gingival Sulcus Irrigation, Master’s thesis, Ann Arbor, The University of Michigan School of Dentistry, 1971. 32. Robinson, L., et al. : Bacteremias of Dental Origin ; Review of the Literature, ORAL SURG. 3: 519. 1950. M. M., and O’Brien, K. P.: Dental Status and Recurrence 33. Croxson, M. S., Altman, of Streptococczcs viridans Endocarditis, L’ancet 1: 1205-1207, 1971. Some Dental Aspects, 34. Jolly, M., and Drucker, D. B. : Prevention of Bacterial Endocarditis; Br. Dent. J. 131: 539-542, 1971. 35. Coflin. F. R.: Subacute Bacterial Endocarditis. Br. Med. J. 2: 571. 1953. and Barnes Mildred W. : Changing Etiology ‘of Bacterial Endocarditis 36. Finland, Maxwell in the Antibacterial Era Ann’Intern. Med. 72: 341-348 1970. ed. 2, St. Louis, i973, The C. V. Mosby Company. 37. Nolte, W. A.: Oral Mi&obiology, p. 14. 38. Khairat, 0.: The Non-aerobes of Postextraction Bacteremia, J. Dent. Res. 45: 1191, 1966. A. A.. Oka. M.. Nakao. K.. and Marauiss. J.: Exaerimental Production of 39. Anerist. Va&ular Lesions by Mechanisms Not Divolving Infection or Sensitivity Factors, Am. J. Pnthol. 36: 181, 1960. 40. Kutscher, A. H., Zegarelli, E. V., and Hyman, G. A.: Pharmacotherapeutics of Oral Disease, New York, 1964, McGraw-Hill Book Company, Inc. 41. Garrison, P. K., and Freedman, L. R.: Experimental Endocarditis; Staphylococcal Endocarditis in Rabbits Resulting From Placement of a Polyethylene Catheter in the Right Side of the Heart, Yale J. Biol. Med. 42: 394-410, 1970.
Oral Rurg. August, 1975 42. Durack, D. T., and Beeson, P. B.: Experimental Bacterial Bndocarditis: Colonization of a Sterile Vegetation, Br. J. Exp. Pathol. 53: 44-49, 1972. 43. Bahn, 8. L., Ross, D., Biencevengx, G., and Behn, A. N.: Experimental Endocarditi,s Induced by Oral Streptococci (Abstr.), J. Dent. Res. 53: SO, 1974. 44. McGowan, 1). S., and Hardie, J. M.: Production of Bacterial Endocarditis in Prepared Rabbits by Oral Manipulation, Br. Dent. J. 137: 129-131, 1974. 45. Limongelli, W. A., Connaughton, B., and Williams, A. C.: Suppurative Osteomyelitis of Mandible Secondary to Fracture, ORAL SURG.38: 850-859, 1974. Beprint requests to: Dr. H. Dean Millard Department of Oral Diagnosis and Radiology The University of Michigan School of Dentistry Ann Arbor, Mich. 48104.
OF MICHIGAN
SCHOOL
D.D.S., MS.,“”
OF DENTISTRY
A retrospective study was done on patients admitted to the University of Michigan Hospital from 1962 to 1972 with a diagnosis of bacterial endocarditis. The findings in the group studied indicate that Streptococcus viridam was the predominant causative organism, males were affected three times as often as females, erythromycin was effective against organisms of oral origin, dental procedures were not definitely established as responsible for the onset of the disease in any of the cases, and rheumatic heart disease and congenital heart disease were the predominant, but not the only, predisposing factors.
B
acterial endocarditis (B.E.) is a serious disease. Despite the amazing progress in modern medicine and the availability of curative antibiotics, the mortality rate of B.E. is quite high. This disease, if cured, may still have disabling sequelae. The average hospitalization period for treatment of B.E. is about 6 weeks, and extensive care and medication are required. Hence, even if the victim of the disease recovers and escapes its sequelae, he has suffered a great financial loss. Recent advances in medicine have lengthened the life-span of many patients susceptible to B.E., so the dentist is being confronted more and more wibh these patients seeking dental care on an outpatient basis. A negligent practitioner may turn a simple dental procedure into a life-threatening situation. That a patient should suffer or even die as the consequence of a simple dental procedure is a tragedy. The purpose of this study was to provide up-to-date information about B.E. useful to the dental profession. The objectives of this study were as follows: 1. To determine predisposing factors to B.E. and find their incidence in the group of patients studied. “Visiting Assistant Professor of Dentistry, Department of Oral Diagnosis and Radiology; Assistant Professor of Dentistry, Department of Oral Diagnosis and Oral Medicine, The lYationa1 University of Iran School of Dentistry, Tehran, Iran. **Professor and Chairman, Department of Oral Diagnosis and Radiology.
219
2. To evaluate predominant causative microorganisms for B.E. and to determine if any change in the causative agents has occurred during recent years. 3. To determine the role of oro-dental conditions and procedures as precipitating factors in B.E. 4. To evaluate the sensitivity of causative microorganisms to selected antibiotics used in the treatment of B.E. 5. To evaluate the mortality rate of B.E. REVIEW OF THE LITERATURE Definition
“Bacterial endocarditis (B.E.) is a microbial infection of the heart valves or of the endocardium in proximity to congenital or acquired cardiac defects.“l Since the infection is caused by a variety of microorganisms (bacterial, mycotic, rickettsial), some have used the term infective endocarditis in the literature.2-” The disease has been classified as subacute bacterial endocarditis (S.B.E.) and acute bacterial endocarditis (A.B.E.) . Subacute bacterial endocarditis generally begins insidiously, occurs on pre-existing heart disease, and is often caused by indigenous organisms with low pathogenicity. Acute bacterial endocarditis begins abruptly, often develops on normal endocardium, is caused by highly pathogenic organisms, pursues a rapid course, and is fulminant.lp 3 Predisposing
factors
Rheumatic heart disease (R.H.D.) is almost universally accepted as the most important and prevalent predisposing factor in S.B.E. This association has been reported with different incidences in various surveys. Dormer8 reported R.H.D. underlying 63 per cent of cases of B.E., Wilkinson’l reported 62 per cent and Finland and Barnes3G found R.H.D. in 46 per cent of B.E. cases. Millard and Tupper” found a relationship between R.H.D. and B.E. in 66 per cent of the cases they studied, and Hobson and Jensen I5 found an 80 per cent relationship in the cases they studied. Congenital heart disease is another established condition predisposing to B.E. and is reported underlying 13.5 to 28 per cent of cases of B.E. in different studies 8, 9, 11,15 A history of rheumatic fever without resultant heart disease has been found in about 2 per cent of S.B.E. cases.” Patients with prosthetic heart valves are very susceptible to B.E.l”, 13,I4316,Ii Arteriosclerotic heart disease is considered to be one of the conditions predisposing to B.E. It has been reported in 4 to 6.5 per cent of B.E. cases.*’ 9, I13In Infective endocarditis has been reported as one of the serious complications of narcotic addiction. Endocarditis in these patients is usually acute and fulminating and involves a normal heart. This infection most commonly affects the right side of the addict’s heart and almost invariably is found in heroin “mainliners” who give themselves multiple daily unsterile intravenous injections.4p I8 Staphylococcus aureus is the most commonly found organism, and Streptococcus
Bacterial
endocarditis
221
viridans is found rarely.3l 4pl8 All of these findings are indicative of the contamination of blood by skin sepsis due to unsterile methods of injection. Precipitating
factors
Any procedure capable of producing bacteremia has the potentiality of precipitating B.E. in a susceptible patient. A bacteremia can be produced by a wide range of different procedures and conditions, such as infections of the upper respiratory tract, orodental conditions and procedures, urinary and gastrointestinal tract infections and manipulations, parturition, abortion, burns, insect bites, surgery, and trauma.ll 3l O Recently the causal relationship between bacteremia and B.E. in abnormal endocardium has been confirmed by experiments on animal models.41-43 Mouth
and
B.E.
As early as the 1920’s suspicion arose about the relation between extraction of infected teeth and heart disease. Calvylg believed that extraction of infected teeth could cause a latent heart infection to flare up. RushtonzO in 1930, reported the production of bacteremia after tooth extraction and discussed the relationship between extraction and S.B.E; Okell and Elliott,21 in 1935, proved the occurrence of transient bacteremia following tooth extraction and found a direct relationship between the incidence of bacteremia, the severity of gingival lesions, and the amount of damage induced during surgery. They reported postextraction bacteremia in 34 per cent of healthy and 75 per cent of septic mouths. Streptococcus viri&n.s was the most common organism in their experiences. in 1939 HopkinP also found Streptococcus viridans to be the most common microorganism in the bloodstream after extraction of teeth. Since then a cause-and-effect relationship between B.E. and teeth has been questioned, and many investigations have been carried out to prove this relationship.23-z5f29The following dental procedures have been shown to produce bacteremia: exodontia,23s*Obrushing the teeth,23 chewing hard candy,23 gingivectomy, scaling and curettage,25t29 endodontic treatment with instrumentation forced beyond the apex,*Oand even ultrasonic scaling.*’ Beers,31using anaerobic and aerobic techniques found pre-extraction bacteremia in dental patients and also in healthy normal controls. In his study extraction caused an increase of the number of bacteria in the bloodstream. Additional support for the relationship between the mouth and B.E. is found in a review of the case histories in which B.E. occurred after dental procedures. Many researchers have found a history of dental procedures preceding B .E .3,5y7-gv***32p33 This association is very hard to prove, especially in cases of S.B.E. The incidence of this relationship has been found with different ratios in the literature. In 1950 Robinson and colleagues3* in a review of the literature, found dental procedures to be implicated in 10.8 per cent of all cases of B.E. Millard and TuppeP found preceding dental procedures in 26 per cent of patients with S.B.E. Croxson and co-workers33 reported this relationship in 40 per cent of patients with B.E. resulting from Xtr. viridans.
It is almost universally are
most
frequently
Oral
Burg.
August,
1975
agreed that B.E. in general and S.B.E. in particular
caused
by
Str.
viri&m~
7 . '2 3, G, 6, R, o, I13 In, 22, 33, 'W 3G Sk.
viridans as a normal inhabitant of the mouth and throat, is the most common microorganism isolated from this area,21 and it also has been found to be the most common microorganism in blood cultures following dental procedurcs.2”-2”~ 27-m Bahn and associates*” have been able to induce B.E. by introducing 8. and X. m&is into the wound socket of an extracted incisor, into the gingiva, or by intravenous injection into the marginal ear vein of the rabbit. The animals were predisposed to B.E. by sterile heart catheterization. The induced endocardial lesions were reported histologically similar to those observed in human B.E. Most recently McGowan and Hardie** produced B.E. in rabbits following dental manipulations after inducing sterile endocardial lesions. m8utans
Prophylactic
measures
for B.E. in dentistry
The first step in prophylaxis is the detection of patients susceptible to endocarditis, and this is carried out by careful history taking.‘* Before performing any dental procedure capable of producing transient bacteremia, the susceptible patients should be premeditated by an appropriate antibiotic regimen.l’ (i Myall and GregoryI believe that even a periodontal examination should be made under an antibiotic cover. Inasmuch as Streptococcus viri&,?as is considered to be the most common cause of B. E. with respect to oral origin, prophylaxis is directed against this organism” in dentistry. However, several other organisms with oral origin have proved to be responsible for B.E., namely, Staphylococci, Enterococci, Candida,? Str. faecalis, and even anaerobic gram-negative rods9 Axelrod and colleagues,12 in 1973, reported a well-documented case of B.E. caused by Lactobacillus 3 weeks after scaling in a previously healthy person. Importance
and mortality
Bacterial endocarditis is a serious disease and, if left untreated, is always fatal.‘9 Ii It has a high mortality rate, even with proper modern therapeutic measures.‘, 6 J)ormer,s in 1958, reported a mortality rate of 43 per cent in patients with B.E., considering early and late deaths. Millard and Tupper,s in 1960, reported a mortality rate of 20 per cent in their survey of patients with S.B.E. In 1971 Neutze and Arte? reported a 42 per cent death rate from B.E. in Green Lane Hospital in New Zealand. The mortality rate of B.E. in patients with valvular prosthesis is much higherI and has been reported up to 77 per cent.lO Financial
loss and sequela
The average hospitalization period for B.E. treatment is 4l to 6 weeks.G During this period, the patient is treated with very high doses of antibiotics, in most cases daily doses of 12 to 20 x 10Gunits of penicillin G and 1.0 Gm. of strept0mycin.l In some cases, even 48 x 10” units of daily penicillin have been used.12 In patients with prosthetic valves, a combination of different anti-
Volume 40 Number 2
Bacterial
I. Incidence 1962-1972
Table
endocarditis
of acute and subacute cases of B.E. studied
Condition
S.B.E. A.B.E. Undetermined B.E. Total
No.
of cases 51 9 4 s4
223
at U.M.H.,
Per cent
79.68 14.06 6.25 100
biotics is necessary.‘3 Considering the expenses necessary for hospitalization, medication, and professional care plus income loss during the course of the disease, the financial loss suffered by the patient is very high. Even if the victim survives, he may suffer from serious crippling sequela, such as hemiparesis, blindness, heart failure, and glomerulonephritis, which are the result of systemic emboli.lp Fl 8$*Is I4 METHOD
OF THE STUDY
Hospital records of patients with the diagnosis of B.E. at the University Hospital in Ann Arbor, Michigan (U.M.H.) for the lo-year period from 1962 to 1972 were selected through the use of computer punch cards. Only those cases that were well documented with the presence of positive blood or valve cultures or cases confirmed by postmortem examination were accepted for the study. Cases with inadequate data were excluded. The following data were collected for each case : 1. Age 2. Sex 3. Race 4. Probable precipitating factor 5. Clinical diagnosis 6. Predisposing factors 7. Dental treatment during hospitalization 8. Blood or valvular culture 9. Sensitivity tests 10. Treatment 11. Recurrence 12. Death 13. Postmortem examination The collected data were analyzed statistically, and some tests of significance were performed in necessary areas. RESULTS
Seventy-eight charts showing a diagnosis of B.E. were retrieved for the lo-year period from 1962 to 1972. During the same period of time, a total of 236,420 patients were admitted to the University Hospital. Thus the incidence of B.E. among other hospital admissions, on the basis of clinical diagnosis, was 0.0329 per cent.
224
Mostnghiw
a)td
Oral August,
Millwd
II. Underlying heart conditions 1T.JI.II. from 1962 to 19i:!
Table
in sixty
patients
with
X0. of patients
Condition
B.E. treatc>d at Per cent
R,.H.D. C.H.D. R.H.D. or C.H.D. undetermined Syphilitic heart disease Arteriosclerotic heart disease Normal
24 12 5 2 2 15
40 20 8.33 3.33 3.33 25
Total
E-l
100
Table
Age distribution
Ill.
Aoe
gro;ps
I
I /
I
II
I /
among B.E. patients III
Age range S.B.E. A.B.E. Undetermined B.E. Total B.E.
0 to 9 10 to 19 20 to 29 2 10 4 L 3
Per cent
10.93
1 7
7 ___ 10.93
- 13 20.31
I /
IV
I j
v
30 to 39 40 to 49 9 8 9 ___ 14.06
2 10 ___ 15.62
at U.M.H., I 1
VI
I 1
1962 to 1972 VII
I 1 VIII
50 to 59 60 to 69 70 to 79 7 4 4 1 I 1 9 14.62--
Surg. 1975
5
4
7.81
6.25
I j Total 51 9 4 64 100
Because of inadequate documentation, eighteen charts were excluded in the final analysis. Four well-documented recurrences occurring during the period of study were added to the sixty documented cases, making a total number of sixty-four cases. Classification
Table I shows the incidence Predisposing
of A.B.E.
versus S.B.E. in the cases studied.
factors
Table II shows the predisposing factors in sixty studied patients. To avoid repetition, the recurrences were not included in this analysis. As it is reflected in the table, R.H.D. was the most prevalent underlying condition and was detected in 40 per cent of the patients. C.H.D. proved to be the second major predisposing condition, with an incidence of 20 per cent, while syphilitic and arteriosclerotic heart disease were each detected in almost 3 per cent of the cases. Twenty-five per cent of the cases occurred on hearts with no previous history of an abnormal condition. The incidence of S.B.E. on normal hearts was 13.72 per cent, while six of nine cases of A.B.E. occurred on normal hearts. In one of the S.B.E. cases and two of the A.B.E. cases occurring on normal hearts the patients were heroin addicts and mainliners. Another patient was diabetic but had no detectable heart involvement. The age distribution is reflected in Table III.
Volume
40
Number
2
Table
Bacterial
IV. Sex distribution
among sixty
at U.M.H.,
No. of cases
Sex
Female Male
-M =
V. Sex distribution
1962-1972 23.33 76.66
60 1
F
225
Per cent
14 46
Total
Table
B.E. patients
endocarditis
100
3.28
among total admissions at U.M.H.
(last 3 years of
study) Sex
No.
Female Male
Per cent
36,935 32,055
Total F -=M
Table
of admissions
VI. Predisposing
53.5 46.5
68,990 1.15
100
1.0
factors to B.E. in females and males seen at U.M.H.,
1962-1972 Female
conclitios
No.
of cases )
R.H.D. C.H.D. R.H.D. or C.H.D. Prosthetic valve Syphilitic H.D. Arteriosclerotic H.D.
-
Total abnormal hearts No. of normal hearts
13 1
Total
ii-
cases
Pm cent
i
I 1 No.
Yale
of uxes (
Per
oewt
17 9 4 -
2 1
: 92.85 100
32 14 46
69.56 100
Sex distribution among B.E. patients studied and total admissions is reflected in Tables IV and V. In an attempt to find an explanation for the discrepancy in sex distribution, the detected organic heart diseases are tabulated in Table VI for each sex group. As it is reflected in the table, the incidence of organic heart diseases was even lower in male patients than in female patients. Addiction
Six of the B. E. patients studied were heroin addicts, all of them “mainliners.” In three cases, B.E. developed on normal hearts. In the remaining three patients B.E. developed over abnormal hearts (R.H.D., syphilitic heart disease, prosthetic valve).
2%
Mostaghim
Table
VII. Etiologic
Oral Surg. August, 1975
and Millard microorganisms
Organisms Streptococci viridans fecalis la&is enterococci liqueficience mitis E:% zymogenes uberus
of B. E., U.M.H.,
19621972 (10 years) No. of cases 19 4 3 2 2 1 1 1
& Y microaerophilic Total Staphylooocd aureus coagulate-negative coagulase-positive microaerophilic Total Miscellaneous Diphtheroids Can&da parapsilosis Cram-negative rods Pneumococci Haemoptilus in&enzae Haemophilus para in&enzae Paracolon Klebsiella Pseudomonas Proteus mirabilis
1 1 2 1 13
Total Total number of organisms
76
Eight organisms were cultured from the blood of these patients : Staphylococci, coagulase-positive Pseudomonas Staphylococcus aureus Str. faecalis Str. viridans Precipitating
3 2 1 1 1
oral factors
Only in nine cases (14.06 per cent) were oral conditions and dental procedures related to the onset of B.E. recorded on the patients’ charts.. They ranged from simple prophylaxis, orthodontic treatment, and tooth capping to root canal therapy, extraction, pericoronitis, and dental abscess. The following microorganisms were cultured from the blood of these patients : 3 Str. viridans 1 Str. l&is 1 Streptococcus, alpha hemolytic
Volume 40 Number 2
Bacterial
Staph. aurew Staphylococcus, microaerophilic Haemophilus para influenzae Klebsiella organisms The interval between dental procedure or infection symptoms ranged from a few days to 8 weeks. Causative
endocarditis
227
1 1 1 1 and the onset of B.E.
microorganisms
The microorganisms isolated from the blood and valve culture of the patients are reflected in Table VII. Seventy-six microorganisms had been isolated from sixty-four cases. Some cases showed multiple causal organisms. In the analysis and discussion, each separate organism is considered one case. Streptococcus viridans proved to be the most common microorganism in this study and accounted for 25 per cent of all the responsible organisms. Str. viridans comprised 37 per cent of the S.B.E. cases (nineteen out of fifty-one). Sensitivity
of microorganisms
to antibiotics
Not all the isolated organisms were subjected to sensitivity tests. All of those tested were not tested against the same combination of antibiotics. With a few exceptions, most of the organisms were tested against penicillin, erythromycin, tetracycline, and streptomycin. Therefore, analysis was performed on these four antibiotics. Although it has been stated that almost every microorganism that has been identified has been isolated at one time or another from the oral cavity,37 it seems reasonable to exclude the remote possibilities and base the analysis on the more probable factors. In this regard, the following organisms were excluded from the data analysis: 1 Paracolon Klebsiella 1 Pseudomonas 2 Proteus mirabilis 1 The above organisms are considered neither indigenous nor supplemental oral flora. Sensitivity
to penicillin
Penicillin-sensitivity tests were done in fifty-nine cases. Forty-one (69.49 per cent) of these organisms were penicillin sensitive. In fifty-five microorganisms of probable mouth origin, forty-one (74.54 per cent) were penicillin sensitive. All Streptococcus viridatzs organisms proved to be penicillin sensitive. The following organisms were either moderately sensitive or resistant to penicillin : Str. famedis 4 cases 1 Peptostreptococcus sp. 2 Staph. aureus
Oral Surg. August, 1975
3 Coagulase-positive staphylococcus 1 Coagulase-negative staphylococcus 1 Haemophillus influenzae 1 Gram-negative rods” 1 Candida’ In three resistant cases (pepto-str., Staph. aureus, coagulase-positive staphylococcus), the patients had been under antibiotic therapy prior to blood culture and sensitivity test, although the nature of the antibiotics was not mentioned in the charts. Sensitivity
to erythromycin
Sensitivity to erythromycin was evaluated in forty-four microorganisms with possible mouth origin. Forty-one (93.18 per cent) cases proved to be erythromycin sensitive. The following were resistant to erythromycin : 1 case Staph. aureus 1 Str. faecalis 1 Candida’ No Str. viridans orga,ni.snw resistant to erythromycin were recorded. Sensitivity
to tetracycline
Sensitivity tests to tetracycline were available on forty-six microorganisms with possible mouth origin. Thirty-six cases (78.20 per cent) were sensitive to tetracycline. The resistant organisms were : 1 case Staph. aureus 1 Coagulase-nqative staphylococcus 5 Str. faecalis 1 Alpha streptococcus 1 Str. viridans 1 Candida” Sensitivity
to streptomycin
Sensitivity tests to streptomycin were available on forty-four microorganisms with probable oral origin. Only twenty-one (47.72 per cent) were streptomycin sensitive. Among thirteen Str. viriclans cases, ten (76.92 per cent) were resistant to streptomycin. That is, only 23.08 per cent of Str. viridans organisms were sensitive to streptomycin. The resistant organisms were : Xtr. viridans 10 cases 5 Str. famecali.s 1 Alpha streptococcus 1 Microaerophilic streptococcus 1 Str. liqueficience 1 Peptostreptococcus sp. 1 Coagulase-positive staphylococcus 1 Coagulase-negative staphylococcus 1 Candida* *Natural
resistance.
Volume Number
40 2
Bacterial
endocarditis
229
Fisher’s exact test was used for statistical comparison between the sensitivity frequencies of penicillin and the other three antibiotics, each pair at a time. The difference between erythromycin and penicillin sensitivities is statistically significant (P = 0.012). The difference between the sensitivities to penicillin and streptomycin is also statistically significant (P = 0.0056). The sensitivity to penicillin was not statistically significantly less than tetracycline (P = 0.421). Mortality
rate
Twenty-one of sixty-four cases ultimately terminated fatally during the 10 years of study. The mortality rate among these patients was 32.8 per cent. There were nineteen cases of Str. ciridnns B.E. in this study. Four of them terminated fatally. Thus, the Str. wiridans mortality rate was 21.5 per cent. DISCUSSION Predisposing
factors
Forty per cent of the patients showed a history of R.H.D. Twenty per cent of the patients had underlying C.H.D. Although the incidence of these two heart diseases as factors predisposing to B.E. was slightly different from that reported in other studies, our findings were in agreement with others in that these were the most frequent heart abnormalities predisposing to B.E.8, g*I1336 Syphilitic and arteriosclerotic heart diseases were each recorded in the history of 3.33 per cent of the patients studied. In former studies the incidence of these two diseases in B.E. patients was reported as being from 4 to 6.5 per cent.8l sl llp l5 In this study, 13.72 per cent of the S.B.E. cases occurred on apparently normal hearts. In the present study, six of the nine A.B.E. cases occurred on normal hearts. This is in agreement with other studies. * In two of the A.B.E. cases on normal hearts, the patients were heroin mainliners. Age
distribution
The incidence of B.E. in some age groups differed not significant statistically (x2 = 7.25, D.F.7, P N 0.6).
slightly,
but this was
Sex distribution
Males were affected more than three times as often as females. This sex predilection was statistically significant when compared to the male : female ratio of total hospital admissions for the last 3 years of the study (x2 = 22, D.F.1, P < 0.001). The reason for this predilection cannot be easily explained. It does not seem to be correlated with the incidence of clinically detectable underlying heart abnormalities. Some unidentified environmental factors may be responsible for this tendency. As the males are subjected to more everyday stresses, stress may play a part in this regard. Angrist and associates3” have produced changes within the valvular tissues of rats under stress and concluded that these nonbacterial endocardial changes could predispose hearts to infection.
Ej-ythj-omyc3n
======P============================== ==============2===5=======-i====~====== ==1===============2======EP==--___-__
-------
93% 80.9%
Estolate !
Stearate Tetracycline
78.26%
================================= ==================-===========z ==I==r====I===========I=========~
88.0% I Penicillin
============================= ============================= =============================
74.52% 76.6%
i-I
I Streptomycin
1
5=================~ -----------__-----======3===1======== -
47.72% ^
L-A
==== ==== Present ==== Pig. 1. Sensitivity of microorganisms 1972) compared with Khairat’s study.3o
r^
Y.b%
Study in bacterial
lIRIIl Khairat’s endocarditis
patients
Study28 (U.M.H.,
196%
Addiction
Six of the patients under study were “heroin mainliners.” Three cases occurred on normal hearts. As the present sample is very small, statistical analysis does not seem to be appropriate Whether or not development of B.E. in addicts is merely due to repeated unsterile intravenous injections remains unanswered on the basis of these data. Precipitating
oral
factors
In only 74 per cent of the cases were oral pathosis and dental procedures assumed to he responsible for the development of B.E. Although the history suggested a close relationship between the oral conditions and the development of B.E. in these patients, judgment is very difficult on the basis of the present data. Although the oral procedures were the only suspicious factors recorded in the history of the patients, other possibilities cannot be ruled out. All but one of the organisms isolated in these pat.ients were among the normal flora of the mouth. The exception was Klebsiella, cultured in a patient with a heart prosthesis 12 days after multiple dental extractions. Although Klebsiella organisms arc not considered to be indigenous or supplemental oral flora, they have occasionally been reported in suppurative dental lesions’” and isolated from postextraction blood cultures.38 In 1960 Millard and Tuppe? reported the incidence of oral conditions as precipitating factors in 26 per cent of S.B.E. patients in this same hospital. Croxson and associates3” in 1971, found this incidence in 40 per cent of B.E. patients. The decrease in the incidence of S.B.E. from an oral source may be the result of improvement of oral health and/or better preventive measures.
Volume Number
40 2
Frequency
Bacterial endocarditis of causative
23 1
microorganisms
Streptococci, especially Str. viridans, proved to be the most frequent causative organisms in this study. This finding is in agreement with all other previous studies.1, 3, 5, 6, 8, 9, 1% 15, 2‘4 33, 34, 36 2%. uiridans was responsible in 25 per cent of BE. and 37 per cent of S.B.E. cases in the present study. Millard and TuppeP reported the incidence of Str. viridans in 64 per cent of S.B.E. cases in this same hospital. The lower incidence of Str. virtians S.B.E. and also the decrease in the incidence of dentally inflicted S.B.E. cases in this study together are strongly suggestive of improvement of oral hygiene and preventive measures. Inasmuch as only nine of the organisms were gram negative, and only four of these may be found in oral flora, and just one was a fungus organism, antibiotics effective against gram-positive organisms may still be considered reliable for B.E. prophylaxis in most dental patients. Sensitivity
In this study, the effects of four currently used antibiotics were evaluated against the isolated microorganisms in vitro. Erythromycin proved to be the most effective agent. Erythromycin was even significantly more effective than penicillin, the universally recommended antibiotic,lv 6 for B.E. prophylaxis in dental procedures. The effect of penicillin and tetracycline did not differ significantly in this study. Streptomycin proved to be the poorest antibacterial agent against the microorganisms cultured within this study. None of the Str. virida,ns organisms was resistant to erythromycin or penicillin. Only one Str. viriclmns strain was resistant to tetracycline, while 77 per cent of the Str. viridans organisms proved to be resistant to streptomycin. Khairat,28 in 1966, evaluated the sensitivity of postextraction blood organisms to twenty-two different antibacterial agents in vitro. He also found erythromycin the most effective of the currently used antibacterial agents. Although the present study and that of Khairat were performed on two completely different groups of pa.tients, the results are very similar. Fig. 1 shows a comparison between the results of these two studies. The close agreement between the two studies cannot be attributed to chance. Tetracycline is a broad-spectrum antibiotic and is effective against both gram-positive and gram-negative organisms, but as the incidence of gramnegative bacteria originating from the mouth is very low, as shown in the present study, there would be no advantage in using tetracycline for S.B.E. premeditation. Still the question remains whether these antibacterial agents are as effective in vivo as they proved to be in vitro. KhairaP compared the effect of intravenous tetracycline and oral tablets of erythromycin as prophylactic covers for
Oral Surg. August,
1975
dental extractions. He conclucicd that intravenous tetracycline was significantl! more effective than oral crythromycin. He attributed this finding to the mow readily available blood concentration through the use of intravenous administration of tetracycline. Considering the above discussion, more in vivo studies would be in order, especially as erythromycin is almost a harmless antibiotic with extremely low toxicity, particularly when used for a short period of time.40 SUMMARY AND CONCLUSIONS Records of the patients with the diagnosis of bacterial endocarditis (B.E.) at the University Hospital in Ann Arbor, Michigan, were drawn out for the IO-year period from 1962 to 1972. Sixty well-documented cases with four reliable recurrences were accepted for the study, and then the collected data were statistically analyzed. The purpose of the study was to evaluate the validity of the present trends in dental prophylaxis against B.E. Analysis of the collected data showed that: 1. B.E. affected males three times as often as females. 2. Rheumatic and congenital heart diseases were the predominant factors predisposing to B.E. 3. Streptococcus vbidn~s was the organism most frequently cultured from the blood of the affected patients. 4. Erythromycin was the most effective antibiotic against the organisms with possible oral origin, in vitro. 5. There was evidence that suggested some oral procedures and infections were responsible for the development of B.E. Conclusive proof of such a cause-and-effect relationship was impossible in this study. A longterm well-planned prospective study is suggested for more reliable conclusions. 6. “Mainlining” by drug addicts has emerged as an important precipitating cause of bacterial endocarditis. 7. The mortality rate among these patients was 32.8 per cent. 8. The mortality rate for B.E. due to Streptococcus viridam was 21.5 per cent. REFERENCES
1. Cluff, L. E., and Fekety, F. R,.: Bacterial Endocarditis. In Harrison’s Principles of Internal Medicine, ed. 6, New York, 1970, McGraw-Hill Book Company, Inc., Vol. 1, pp. 767-770. 2. Thayer, W. S.: Bacterial or Infective Endocarditis, Edinburgh Med. J. 38: 237-265, 307-334. 1931. 3. Lerner,’ Philip, and Weinstein, Louis: Infective Endocarditis in the Antibiotic Era, N. Engl. J. Med. 274: 199-206, 1966. 4. Cherubin, C. E., et al.: Infective Endocarditis in Narcotic Addicts, Ann. Intern. Med. 69: 1091-1098, 1968. 5. Salma!, Laurence, William, F. H., and Palladina, V. 5.: Fatal Bacterial Endocarditis Followmg Tooth Removal, ORAL SURG. 30: 749-754, 1970. 6. American Heart Association: Prevention of Bacterial Endocarditis, J. Am. Dent. Assoc. 85: 1377-1379, 1972. 7. Neutze, J. M., and Arter, W. 5.: Bacterial Endocarditis and the Dentist, N. Z. Dent. J. 67: 79-84, 1971.
Bacterial
endocarditis
233
8. Dormer, A. Eric: Bacterial Endocarditis; Survey of Patients Treated Between 1945 and 1956, Br. Med. J. 1: 63-69, 1958. 9. Millard, H. D., and Tupper, C. J.: Subacute Bacterial Endocarditis; a Clinical Survey, J. Oral Surg. 18: 224-229, 1960. 10. Shafer, R. B., and Hall, ‘Wendel: Bacterial Endocarditis Following Open Heart Surgery, Am. J. Cardiol. 25: 602-606, 1970. Il. Wilkinson, Matthew: Bacterial Endocarditis and Focal Infection, Dent. Pratt. 17: 201-204, 1967. 12. Axelrod, Judith, et al.: Endocarditis Caused by Lnctobncdlus plantnrum, Ann. Intern. Med. 78: 33-37. 1973. 13. Archard, H. O:, and Roberts, W. E.: Bacterial Endocarditis After Dental Procedures in Patients With Aortic Valve Prosthesis, J. Am. Dent. Assoc. 72: 648-652. 1966. 14. Myall, R. W., and Gregory, H. S.: Current Trends in Prevention of Bacterial Endocarditis in Susceptible Patients Receiving Dental Care, ORAL SURG. 28: 813-818, 1969. 15. Hobson. F. G.. and Jensen. B. E. J.: Teeth. Strentoooccus viridnns and Subacute Bacterial Endocarditis, br. Med. J. i: 1501-1505, 1956. A 16. Bottomley, W. K., Willis, P. W., and Fekety, F. R.: The Dental Patient With a Heart Valve Prosthesis; Preoperative and Postoperative Conditions, Mich. Dent. Assoc. J. 51: 149-151, 1969. 17. Tanenbaum, Considerations in Patients With Prosthetic Heart H. L.: Prophylactic Valves Undergoing Dental Procedures, Med. Ann. D. C. 41: 457-458, 1972. 18. Menoa, K. B., and Gorbach, S. L.: Favorable Experience With Bacterial Endocarditis in Heroin Addicts, Ann. Intern. Med. 78: 25-32, 1973. 19. Calvy, P. J.: Dental Surgery and Organic Heart Disease, J. A. M. A. 74: 1221, 1920. 20. Rushton. M. A.: Subacute Bacterial Endocarditis Followins Extraction of Teeth and Tonsils,‘Guy’s Hosp. Rep. 80: 39-44, 1930. 21. Okell,. C. C., and Elliott, S. D.: Bacteremia and Oral Sepsis; With Special Reference to Etiology of Subacute Endocarditis, Lancet 2: 869-872, 1935. 22. Hopkins, J. A.: Streptococcm wiridans Bacteremia Following Extraction of Teeth, J. Am. Dent. Assoc. 26: 2002. 1939. Bacteremia, ORAL Suao. 7: 609, 1954. 23. Cobe, H. M.: Transistory 24. Varaas, B., et al.: Effects of Certain Factors on Bacteremias Resulting From Gingival Resection, J. Periodontol. 30: 796-207, 1959. M. B., and Kobernick, 8. D.: Bacteremia After Prophylaxis, J. Am. Dent. 25. Winslow, Assoc. 61: 69, 1960. 26. Bender, I. B., et al.: Dental Procedures in Patients With Rheumatiic Heart Disease, ORAL SURG. 16: 466, 1963. and Hand 27. Bandt. C. L.. Korn. N. A.. and Schaffer. E. M.: Bacteremias From Ultrasonic Instru’mentation, J.‘Periodbntol. 35: 214,’ 1964. 28. Khairat, 0. : An Effective Antibiotic Cover for Prevention of Endocarditis Following Dental and Other Postouerative Bacteremias. J. Clin. Pathol. 19: 561-566. 1966. Foll&ing Periodontal Scaling ‘in Patients With 29. Conner, H. D., et al:: Bacteremia Healthy Appearing Gingiva, J. Periodontol. 38: 466-472, 1967. 30. Tamimi, H. A., Thomassen, P. R,., and Moser, E. H., Jr.: Baeteremia Study Using a Water Irrigation Device, J. Periodontol. 40: 424.426, 1969. 31. Beers, Royce L.: Reduction of Dental Extraction Bacteremias by Gingival Sulcus Irrigation, Master’s thesis, Ann Arbor, The University of Michigan School of Dentistry, 1971. 32. Robinson, L., et al. : Bacteremias of Dental Origin ; Review of the Literature, ORAL SURG. 3: 519. 1950. M. M., and O’Brien, K. P.: Dental Status and Recurrence 33. Croxson, M. S., Altman, of Streptococczcs viridans Endocarditis, L’ancet 1: 1205-1207, 1971. Some Dental Aspects, 34. Jolly, M., and Drucker, D. B. : Prevention of Bacterial Endocarditis; Br. Dent. J. 131: 539-542, 1971. 35. Coflin. F. R.: Subacute Bacterial Endocarditis. Br. Med. J. 2: 571. 1953. and Barnes Mildred W. : Changing Etiology ‘of Bacterial Endocarditis 36. Finland, Maxwell in the Antibacterial Era Ann’Intern. Med. 72: 341-348 1970. ed. 2, St. Louis, i973, The C. V. Mosby Company. 37. Nolte, W. A.: Oral Mi&obiology, p. 14. 38. Khairat, 0.: The Non-aerobes of Postextraction Bacteremia, J. Dent. Res. 45: 1191, 1966. A. A.. Oka. M.. Nakao. K.. and Marauiss. J.: Exaerimental Production of 39. Anerist. Va&ular Lesions by Mechanisms Not Divolving Infection or Sensitivity Factors, Am. J. Pnthol. 36: 181, 1960. 40. Kutscher, A. H., Zegarelli, E. V., and Hyman, G. A.: Pharmacotherapeutics of Oral Disease, New York, 1964, McGraw-Hill Book Company, Inc. 41. Garrison, P. K., and Freedman, L. R.: Experimental Endocarditis; Staphylococcal Endocarditis in Rabbits Resulting From Placement of a Polyethylene Catheter in the Right Side of the Heart, Yale J. Biol. Med. 42: 394-410, 1970.
Oral Rurg. August, 1975 42. Durack, D. T., and Beeson, P. B.: Experimental Bacterial Bndocarditis: Colonization of a Sterile Vegetation, Br. J. Exp. Pathol. 53: 44-49, 1972. 43. Bahn, 8. L., Ross, D., Biencevengx, G., and Behn, A. N.: Experimental Endocarditi,s Induced by Oral Streptococci (Abstr.), J. Dent. Res. 53: SO, 1974. 44. McGowan, 1). S., and Hardie, J. M.: Production of Bacterial Endocarditis in Prepared Rabbits by Oral Manipulation, Br. Dent. J. 137: 129-131, 1974. 45. Limongelli, W. A., Connaughton, B., and Williams, A. C.: Suppurative Osteomyelitis of Mandible Secondary to Fracture, ORAL SURG.38: 850-859, 1974. Beprint requests to: Dr. H. Dean Millard Department of Oral Diagnosis and Radiology The University of Michigan School of Dentistry Ann Arbor, Mich. 48104.
