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Subacute bacterial endocarditis successfully treated with penicillin
SUBACUTE
F
BACTERIAL TREATED
ENDOCARDITIS SVC!CESSFULTIY WITH PRYIC!JI,CTN
H. J., a Z;l-year-old white ulan, was incarcerated in the United St,ates Northeastern Penitentiary, Lewisburg, Pa.? on Oct. 4, 1914. Ire was assigned to the work of He worked steadily at this job for handling steel on the night shift of piison industries. slightly more than three months. On the evening of *Tan. 13, 1015, he reported to the prison hospital, complaining of shortness of breath and palpitation of three days’ duration. He stated that he had “Iow blood pressure ” and that six months previously an Army Further questioning reinduction board had classified him 1F lmcause of this condition. vealed that he had had acute rheumatic fever at the age of II and again at the age of 16 years. At the age of 27 years a fainting spell led to several weeks’ hospitalization. He was told by his attending physician at that time that he had suffered a heart attack. l
The patient was therefore admitted to the prison hospital for study. I’pon admission he appeared well developed and well nourished and n-as in no acute distress, His weight was 152 pounds. II0 was ambulatoryand well oriented. ‘I’ht temperature X:IS OS” F.. th(L pulse was 100, and the respirations were JO per minute. The blood pressure was 13-l/50. The skin was sallow. There was no lgmphadenopal hy. The eyes sho\ve(l an old chorioiditis. There was extensive gingivitis and dental caries. Examination of the heart rerealrd a forceful apex thrust in the fifth intercostal space I:! cm. to the left of the midline; there were no palpable thrills; the rate was 100, with :I regular rhythm. The apical first sound was accentuated and roughened, followed immediately by a short highpitched systolic murmur. The sortie second sound was muffle11 and partially ohacured by a to-aud-fro systolic and diastolic murmur which was transmitted into the neck vessels. There was no ankle edema, no hepatic engorgement, no distention of the jugular veins, and no rkles in the lung bases. Duroziez’s sign was ecpril-ocal. An electrocardiogram showed widening of the QRS in all leads, inverted P,, deep QB, inverted T, and ‘i’>> elevated RR-T,. depressed RS-T,, au11 left axis deviation. A teleroentgenogram of the chest showed the lreart to 1~ at the uppci limit of normal size, with slight prominence of the left veilt ricle. The patient was observed for two nceks. Durin g this time he was ambulatory, slept without difficulty on one pillow, remained entirely afebrile, and had no complaints. on -Tan. 31, 194.5, when arrangements with the prison administration for sedent:rr,y occupation had been completed, he was discharged. The diagnosis on discharge was inactive rhea matic heart disease with aortic stenosis and insufficiency anrl possible early mitral insufficicnc~. Xine days later, the patient again reported to the hospital complaining of a co111 and sore throat n-hich had been present for the preyions forty-eight hours. Fever and pains in the hips, knees, ankles, and \\-rists had csistel ! for lwent>--four hours. Rsamination revealed: temperature, ICJII; pulse rat,‘, lil0; respirntil,n. 2-i; IllOOll ,l’ess”re, 1::4,.‘.w. Till, skin was warm and flushed, but there were no petechiae. The cervical lymph nodes xvere shotty and tender. The pharyngeul mucous membranes were injected. The left ankle and right hip were tender to touch but were not \varm, reddened, or svvollen. The cardiac findings were the same as had been noted previously. The blood count showed: red blood cells, 5,300,OOO; l~en~oglol~in, 12.6 Gm.; white 1)lood cells, 8.250; polys, 64 per g:ent. lymph Received *Senior
for publication July 5, 13 15. Assistant Surgeon, U.S.P.H.S., CJnited 6.51
States
Penitentiary
Hospital.
‘J’ht~ sedimentation ncytes, 21 per cent: monocytes, 13 per cent; ~9xGnophilt~s. L’ ~aer t’ent. rate (Wintrohe) was 37 nun. per hour. ‘l’htb urinalysis V:L,G negative>. The patient was admitted to the hospital with a tentative diagnosis of an acutta cxxccrbation of rheumatic fe:-er. Hc was put to lbed and given full doses of .sndiurn ,sdi(*~l:~te, whicah relieved thy l~r)wc\-er, the fever still pel joint symptoms. After ten days of symptom:Ltic therap!-, sisted, averaging 100.4” 1’. The pulse consistently remained over 100. A blood c~ulturt~ taken on the thirteenth hospital day. showed on the eighteenth (lay a Imrc 4turc ot streptococcus viridans with right colonies per cubic centirneicr. .\ rrcond 4ture, taken ngain positive for streptncocc11s viridans. ‘I’hrcc additionnl on the twentieth day, was cultures taken prior to the adllrinistr:ltior1 of pt~nicillin w~rc nlso positirr,. On the twenty-fifth hospital day, c:ar(liac* Iahan,C,cr.* were first erident; g diastolic murmur were tletected 31 the apex; itncl a lowpitched rumblin murmur had become longer; the blood pressure was 134/10.
a diastolic thrill npicnl systoli~~
the
On the thirty-second hoqital day the patient, developetl in hid lrft conjunctiva his first and only petechin. The following day ho suddenly developed severe prrscnrdial pain radiating to the left axills; his left arm suddcnlp bct~nrn~~ nllmb and partially pxralyzcd. TTse of the arm returned slowly over a ten-(laperiod. In vitro sensitivity tests wer(’ Penicillin therapy was started on the thirty-sixth day. made at the beginning of penicillin therally in the following manner: d loopful of a forty-eight-hour broth ~~ulturt~ of the patient’s blood was inoculated into each of several flasks of l)rain-heart infusion broth containing penicillin in concentrations ranging from 0.0005 unit per cubic centimetc,r 1.0 0.5 Oxford unit per cubic ciantimeter. After a seventy-two-hour inculpation periud it was found that there was complctc~ inhibitioll of growth of the organisms in those fktsks whosc~ I)enicillin concentration was 0.05 unit per cubic centimeter or greater. while growth was noted in all flasks whose penicillin concentration was lower than 0.05 unit per cubic centimeter. During the first ninety-six hour?, iin,lKM units of penicillin were given b\- continuous intravenous drip. Each 100,000 units wtbrt’ dissol\ell in I I,. of 5 per cent dextrose in distilled water. Because of thca severe 11~~:~l re:~rtion! however, the penicillin was administered intramuscularly, 3(1,flrN units I)eirlg givtln el-cry three hours for three days. Thrb dosage was then lowered to 15,0110 units +l\-ery three hours and was maintained at this rate for three days but, because of a slight afttarnoon temperatnre rise with the smaller dose, was then raised to 20,000 units every three hours. This dosage was continued for eight units pvclry three hours for five and one-half days. days and then increased to 30.000 Although 3,110,OOO units were given int r:rtn~isc,nl:c~l,v, the patient tolerated thr injectionk4 c~xtrernely well. .2 concentration of 10,001) units per cubic: centimeter was employed. When treatment wus terminate~l. on tltca fifty-eighth da)-, :L total of -1.~10,000 units had lwen given routinuousl>over it twenty-thrccb and ontn-halt’ day pr~rir)~I. After, six tlays of treatment the tc’t’t h wrre x-r:cyc>tl. .\I1 :Itrscess was f~llUld nt thaw root of the 1owc.r right, Jirst bicuspi~l. ‘I’~I~ tooth way rstral~tcd. lxll unfortun;ttrlv no (‘IIItnre was taken from the abscess. lilooti cultures which, before treatment, had been persistently positive for Strepto COCCU.S riri~lctns, became sterile twenty-four hours after the initiation of treatment. Cultures taken every seventy-two hours during the administration of penicillin and al welsk1.v inter vals since, have lleen sterile to date. Ye\-PU week;; have ~1:1pwl pence t r’r:at rrlfant w;c;i discontinued. The temperature, which had averaged 1110.4’ I’. I’riur tu the initiation of penicillin therapy, fell rapidly to normal and remained normal caxcept for afternoon rises of less than 1” k’. After nine days of therapy the patient became completely afebrile and has remaineli Ttlr Ilulse likewise slowed from between 100 and 110 to bet--een 80 and RO? and r(‘W. mained :IL this rate even when the patient became ambulatory. The diastolic blood prepsure, which had fallen from its original level of 50 mm. to 10 mm., rose gradually and at the termination of therapy stood again at 50 millimeters. Likewise, the diastolic apical bruit which developed during the first part of hospitalization diminished in intensity con-
1IOUROF jI
1:
PE:KICILI,IS
IX
SUHACCTE
RACTERIAL
ESDOCARDITIS
653
siderably
during and after treatment. It seems most likely that this represented a true Flint’s murmur, particularly since a very recent teleroentgenogram of the heart showed no changa iu size or shape of the left auricle as compared with the previous picture that would indicate the development of mitral stenosis. The patient’s weight, which had fallen from 182 pounds on a
At the t,irne of his discharge from prison, in March, 1946, t.he patient still bacteriologically negative.
was
F
BACTERIAL TREATED
ENDOCARDITIS SVC!CESSFULTIY WITH PRYIC!JI,CTN
H. J., a Z;l-year-old white ulan, was incarcerated in the United St,ates Northeastern Penitentiary, Lewisburg, Pa.? on Oct. 4, 1914. Ire was assigned to the work of He worked steadily at this job for handling steel on the night shift of piison industries. slightly more than three months. On the evening of *Tan. 13, 1015, he reported to the prison hospital, complaining of shortness of breath and palpitation of three days’ duration. He stated that he had “Iow blood pressure ” and that six months previously an Army Further questioning reinduction board had classified him 1F lmcause of this condition. vealed that he had had acute rheumatic fever at the age of II and again at the age of 16 years. At the age of 27 years a fainting spell led to several weeks’ hospitalization. He was told by his attending physician at that time that he had suffered a heart attack. l
The patient was therefore admitted to the prison hospital for study. I’pon admission he appeared well developed and well nourished and n-as in no acute distress, His weight was 152 pounds. II0 was ambulatoryand well oriented. ‘I’ht temperature X:IS OS” F.. th(L pulse was 100, and the respirations were JO per minute. The blood pressure was 13-l/50. The skin was sallow. There was no lgmphadenopal hy. The eyes sho\ve(l an old chorioiditis. There was extensive gingivitis and dental caries. Examination of the heart rerealrd a forceful apex thrust in the fifth intercostal space I:! cm. to the left of the midline; there were no palpable thrills; the rate was 100, with :I regular rhythm. The apical first sound was accentuated and roughened, followed immediately by a short highpitched systolic murmur. The sortie second sound was muffle11 and partially ohacured by a to-aud-fro systolic and diastolic murmur which was transmitted into the neck vessels. There was no ankle edema, no hepatic engorgement, no distention of the jugular veins, and no rkles in the lung bases. Duroziez’s sign was ecpril-ocal. An electrocardiogram showed widening of the QRS in all leads, inverted P,, deep QB, inverted T, and ‘i’>> elevated RR-T,. depressed RS-T,, au11 left axis deviation. A teleroentgenogram of the chest showed the lreart to 1~ at the uppci limit of normal size, with slight prominence of the left veilt ricle. The patient was observed for two nceks. Durin g this time he was ambulatory, slept without difficulty on one pillow, remained entirely afebrile, and had no complaints. on -Tan. 31, 194.5, when arrangements with the prison administration for sedent:rr,y occupation had been completed, he was discharged. The diagnosis on discharge was inactive rhea matic heart disease with aortic stenosis and insufficiency anrl possible early mitral insufficicnc~. Xine days later, the patient again reported to the hospital complaining of a co111 and sore throat n-hich had been present for the preyions forty-eight hours. Fever and pains in the hips, knees, ankles, and \\-rists had csistel ! for lwent>--four hours. Rsamination revealed: temperature, ICJII; pulse rat,‘, lil0; respirntil,n. 2-i; IllOOll ,l’ess”re, 1::4,.‘.w. Till, skin was warm and flushed, but there were no petechiae. The cervical lymph nodes xvere shotty and tender. The pharyngeul mucous membranes were injected. The left ankle and right hip were tender to touch but were not \varm, reddened, or svvollen. The cardiac findings were the same as had been noted previously. The blood count showed: red blood cells, 5,300,OOO; l~en~oglol~in, 12.6 Gm.; white 1)lood cells, 8.250; polys, 64 per g:ent. lymph Received *Senior
for publication July 5, 13 15. Assistant Surgeon, U.S.P.H.S., CJnited 6.51
States
Penitentiary
Hospital.
‘J’ht~ sedimentation ncytes, 21 per cent: monocytes, 13 per cent; ~9xGnophilt~s. L’ ~aer t’ent. rate (Wintrohe) was 37 nun. per hour. ‘l’htb urinalysis V:L,G negative>. The patient was admitted to the hospital with a tentative diagnosis of an acutta cxxccrbation of rheumatic fe:-er. Hc was put to lbed and given full doses of .sndiurn ,sdi(*~l:~te, whicah relieved thy l~r)wc\-er, the fever still pel joint symptoms. After ten days of symptom:Ltic therap!-, sisted, averaging 100.4” 1’. The pulse consistently remained over 100. A blood c~ulturt~ taken on the thirteenth hospital day. showed on the eighteenth (lay a Imrc 4turc ot streptococcus viridans with right colonies per cubic centirneicr. .\ rrcond 4ture, taken ngain positive for streptncocc11s viridans. ‘I’hrcc additionnl on the twentieth day, was cultures taken prior to the adllrinistr:ltior1 of pt~nicillin w~rc nlso positirr,. On the twenty-fifth hospital day, c:ar(liac* Iahan,C,cr.* were first erident; g diastolic murmur were tletected 31 the apex; itncl a lowpitched rumblin murmur had become longer; the blood pressure was 134/10.
a diastolic thrill npicnl systoli~~
the
On the thirty-second hoqital day the patient, developetl in hid lrft conjunctiva his first and only petechin. The following day ho suddenly developed severe prrscnrdial pain radiating to the left axills; his left arm suddcnlp bct~nrn~~ nllmb and partially pxralyzcd. TTse of the arm returned slowly over a ten-(laperiod. In vitro sensitivity tests wer(’ Penicillin therapy was started on the thirty-sixth day. made at the beginning of penicillin therally in the following manner: d loopful of a forty-eight-hour broth ~~ulturt~ of the patient’s blood was inoculated into each of several flasks of l)rain-heart infusion broth containing penicillin in concentrations ranging from 0.0005 unit per cubic centimetc,r 1.0 0.5 Oxford unit per cubic ciantimeter. After a seventy-two-hour inculpation periud it was found that there was complctc~ inhibitioll of growth of the organisms in those fktsks whosc~ I)enicillin concentration was 0.05 unit per cubic centimeter or greater. while growth was noted in all flasks whose penicillin concentration was lower than 0.05 unit per cubic centimeter. During the first ninety-six hour?, iin,lKM units of penicillin were given b\- continuous intravenous drip. Each 100,000 units wtbrt’ dissol\ell in I I,. of 5 per cent dextrose in distilled water. Because of thca severe 11~~:~l re:~rtion! however, the penicillin was administered intramuscularly, 3(1,flrN units I)eirlg givtln el-cry three hours for three days. Thrb dosage was then lowered to 15,0110 units +l\-ery three hours and was maintained at this rate for three days but, because of a slight afttarnoon temperatnre rise with the smaller dose, was then raised to 20,000 units every three hours. This dosage was continued for eight units pvclry three hours for five and one-half days. days and then increased to 30.000 Although 3,110,OOO units were given int r:rtn~isc,nl:c~l,v, the patient tolerated thr injectionk4 c~xtrernely well. .2 concentration of 10,001) units per cubic: centimeter was employed. When treatment wus terminate~l. on tltca fifty-eighth da)-, :L total of -1.~10,000 units had lwen given routinuousl>over it twenty-thrccb and ontn-halt’ day pr~rir)~I. After, six tlays of treatment the tc’t’t h wrre x-r:cyc>tl. .\I1 :Itrscess was f~llUld nt thaw root of the 1owc.r right, Jirst bicuspi~l. ‘I’~I~ tooth way rstral~tcd. lxll unfortun;ttrlv no (‘IIItnre was taken from the abscess. lilooti cultures which, before treatment, had been persistently positive for Strepto COCCU.S riri~lctns, became sterile twenty-four hours after the initiation of treatment. Cultures taken every seventy-two hours during the administration of penicillin and al welsk1.v inter vals since, have lleen sterile to date. Ye\-PU week;; have ~1:1pwl pence t r’r:at rrlfant w;c;i discontinued. The temperature, which had averaged 1110.4’ I’. I’riur tu the initiation of penicillin therapy, fell rapidly to normal and remained normal caxcept for afternoon rises of less than 1” k’. After nine days of therapy the patient became completely afebrile and has remaineli Ttlr Ilulse likewise slowed from between 100 and 110 to bet--een 80 and RO? and r(‘W. mained :IL this rate even when the patient became ambulatory. The diastolic blood prepsure, which had fallen from its original level of 50 mm. to 10 mm., rose gradually and at the termination of therapy stood again at 50 millimeters. Likewise, the diastolic apical bruit which developed during the first part of hospitalization diminished in intensity con-
1IOUROF jI
1:
PE:KICILI,IS
IX
SUHACCTE
RACTERIAL
ESDOCARDITIS
653
siderably
during and after treatment. It seems most likely that this represented a true Flint’s murmur, particularly since a very recent teleroentgenogram of the heart showed no changa iu size or shape of the left auricle as compared with the previous picture that would indicate the development of mitral stenosis. The patient’s weight, which had fallen from 182 pounds on a
At the t,irne of his discharge from prison, in March, 1946, t.he patient still bacteriologically negative.
was