Battle Casualties in Korea: Studies of the Surgical Research Team, Volume IV
Staphylococcal Bacteremia: Report of a Case SuccessfullyTreated With Erythromycin*
First Lieutenant Fred D. Parrott, MSC, USAR
Captain John B. Selby, MC, USA
Captain Carl M. Pearson, MC, USAR
Recent data indicate that there is an increasing number of staphylococcus strains resistant to chemotherapeutic agents. Two cases of acute bacterial endocarditis due to hemolytic Staphylococcus aureus, which ended fatally despite treatment with virtually all the antibiotics except erythromycin, were reported by Carmichael.1 In Boston City Hospital, about 75 per cent of the 500 strains of hemolytic, coagulase-positive staphylococci were resistant to penicillin, 25 per cent to aureomycin and 33 per cent to oxytetracycline (Terramycin). Finland and Haight2 felt that the widespread use of antibiotics is probably of great importance in this increase of resistant staphylococci and other bacteria. Pulaski et al.3 have noted that a decrease in penicillin-sensitive strains of Staphylococcus aureus closely parallels uncontrolled cross infection. Sherris and Florey4 observed a distinct correlation between the clinical manifestations and the penicillin sensitivity of the causative staphylococci. While deep-seated infections were usually associated with penicillin-sensitive staphylococci, penicillin-resistant staphylococci were principally found in superficial lesions.
The problem of drug-resistant pathogenic staphylococci was recentlyencountered by us in a seriously injured man, who had in addition to multiplefractures and renal insufficiency, a bacteremia due to a staphylococcuswhich proved to be resistant to all of the routinely used antibiotics.It is our distinct impression that the improvement in his clinical coursecoincided with the administration of a new antibiotic, erythromycin,5and because of this we feel justified in accrediting to this agent a majorshare in his ultimate survival. Erythromycin is derived from Streptomyceserythreus, and is a broad-spectrum antibiotic, most active againstgram-positive and less against gram-negative or-
*From the Renal Insufficiency Center, 11th Evacuation Hospital, Wonju, Korea. Reprinted from American Practitioner and Digest of Treatment, July 1954, Vol. 5, No. 7. Copyright 1954 by J. B. Lippincott Company, Philadelphia.
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ganisms.6 It is also said to be effective against rickettsioses,viral pneumonia and infections with Corynebacteria and Clostridia.Its spectrum in general parallels that of penicillin, but its high effectivenessagainst staphylococci, including those resistant to other antibiotics,may make it a valuable adjunct to the antibiotic armamentarium.
Case Report
A 25-year-old soldier was injured in a truck accident in Korea on thenight of April 1, 1953. When taken to a clearing company, he was in shock.Despite treatment, he was still in shock when admitted to the 46th ArmySurgical Hospital. There he was given 3,000 cc. of blood, 500 cc. of dextran,and norepinephrine. His blood pressure gradually rose to 100/40 mm. Hg.and following an additional 1,500 cc. of blood the pressure stabilizednear 150/98 mm. Hg. The urinary output for the first 12 hours after admissionwas only 11 cc., despite the maintenance of an adequate blood pressure.
Thus, on April 3, 36 hours after injury, he was transferred to the renalinsufficiency unit of the 11th Evacuation Hospital. The surgical diagnosiswas a simple fracture of the left humerus and a compound fracture of theleft mid-femur. A hip-spica was applied to the latter which was treatedas a closed fracture because the open wound was thought to have been producedby bone puncture from within.
Initial antibiotic treatment consisted of 600,000 units of penicillinand 0.5 gm. streptomycin daily. The temperature ranged from 99 to 101°F. Renal insufficiency persisted and uremia and hyperpotassemia becameprogressively more severe. On April 8 he was subjected to dialysis on theartificial kidney for 6 hours. Uremia and serum potassium elevation, however,rapidly recurred, now with 347 mg. per cent serum nonprotein nitrogen and8.8 mEq. per liter serum potassium. A second hemodialysis was performedon April 12. Following this he developed acute pulmonary edema and signsof a pulmonary process, probably of infectious nature, in the left upperlobe. At this time streptomycin was discontinued and chloramphenicol, 2gm. daily, started along with penicillin.
A third dialysis on the artificial kidney became necessary and was successfullyperformed on April 17. Following this diuresis began, and on April 20 exceededfor the first time, 1,000 cc. per day. There were no further signs of renaldysfunction. Due to the critical state, no attempts were made until thento deal with the fracture sites despite the realization that the surroundingnecrotic tissue was playing a part in the recurrent rapid elevation ofthe serum nonprotein nitrogen and potassium. The patient appeared to beprogressing satis-
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factorily when on April 20 he developed a chill and fever, and his temperaturerose to 104° F. A blood culture at this time yielded a hemolytic staphylococcus.Six more blood cultures taken during the next 7 days also yielded the sameorganism. A chest roentgenogram at this time showed a cystic pneumonitiswith probable abscess formation in the left upper lobe. The site of thefracture of the left thigh was swollen and tender. Cultures taken fromthe bloody drainage revealed a hemolytic staphylococcus and Pseudomonasaeruginosa (Bacillus pyocyaneus).
The staphylococcus was tested for its susceptibility to six antibiotics,using Difco discs and by the serial tube dilution method. It was resistantto terramycin, 60 mcg.; dihydrostreptomycin, 100 mcg.; aureomycin, 60 mcg,;and bacitracin, 20 units; with both methods. In the tube tests, it wasresistant to penicillin, 50 units; and sensitive to chloramphenicol, 10mcg., as well as to 2 mcg. erythromycin per cc. medium.
Thus, on April 24, 1953, penicillin was discontinued and chloramphenicol(0.5 gm. intravenously b. i. d. and 0.5 gm. orally q. i. d.) was given.The patient's condition, however, continued to be more and more critical,despite the large amounts of chloramphenicol received. The temperatureranged between 103° and 105° F. and a toxic psychosis developed.Severe dyspnea and tachycardia persisted. All daily blood cultures takenduring this period revealed hemolytic staphylococci.
On April 27, 1953, a supply of erythromycin was obtained.* The patientwas immediately started on 2 gm. and later given 4 gm. per day, while chloramphenicolwas discontinued. The daily blood cultures taken thereafter were negative,and continued to be so throughout the remainder of the patient's illness.On April 30, aqueous penicillin, one million units every 2 hours (12 millionunits daily), was begun and later Gantrisin was also added. Following thisthe fever fell gradually, the toxic psychosis slowly cleared, and the roentgenologicevidence of pneumonitis lessened. Recovery was slow.
At no time during the course of the patient's illness was there a definitivecardiac murmur heard, but at the height of illness a coarse, pericardialfriction rub was detected. On May 10, the clinical condition had improvedsufficiently so that the patient was evacuated to Japan, continuing onthe previous antibiotic regime at the Tokyo Army Hospital, where for about45 days the patient was on an antibiotic schedule of erythromycin, 2 gm.daily; penicillin, 15 to 32
*The erythromycin was obtained through the courtesy of Dr. J. W. Smith of the Medical Department, Eli Lilly and Company.
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million units daily (given by combined intravenous and intramuscularroutes); streptomycin, 2 gm. daily; and Gantrisin orally, 6 gm. daily.Between May 10 and June 4 the temperature ranged from 98.6° to 100.4°F., and subsequently remained normal for 30 days. Blood cultures takenduring this period remained sterile. On May 23, a culture of the necroticmaterial near the fracture of the femur revealed Pseudomonas aeruginosabut no staphylococci. On May 27, the necrotic tissues were débrided.This was followed by a brief period of shock. Upon recovery, more rapidimprovement ensued, although a tachycardia persisted. On June 30, all antibioticswere discontinued and the patient remained afebrile. The fracture siteswere healing; his appetite had returned and he is beginning to regain someof his considerable weight loss.
Discussion
In this case, Staphylococcus aureus bacteremia persisted for7 days in spite of treatment with penicillin and chloramphenicol. The bloodcultures became sterile, however, immediately after the beginning of erythromycinmedication. In vitro sensitivity testing confirmed the clinicalimpression that erythromycin was the most effective antibiotic againstthis strain of staphylococcus. The origin of the staphylococcal bacteremiaremained in doubt, but it is likely that there were multiple infected fociin the lung and in the necrotic tissues about the fractured left femur.An acute bacterial endocarditis was neither ruled out nor confirmed.
It is impossible to ascertain what effect the additional antibiotics,given later in the illness in conjunction with erythromycin, had on theultimate recovery. Certainly, there was no evidence of antibiotic antagonism.On the contrary, a synergistic effect may be suspected in this case. Becauseof the close similarity in the antibacterial spectra of penicillin anderythromycin, it seems logical to presume that each may have played somerole in the suppression of this infection, especially in view of the largedoses of penicillin that were utilized.
Summary
A seriously injured man who suffered from multiple fractures, bloodloss, shock, and severe renal insufficiency necessitating three artificialhemodialyses, with a virulent staphylococcal bacteremia, was eventuallybrought back to health by a prolonged series of therapeutic procedures.The hemolytic Staphylococcus aureus isolated from this case wasresistant to the routinely used antibiotics in vitro, but was verysensitive to erythromycin. Recovery, although slow, could be dated fromthe time that treatment with erythromycin was begun.
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References
1. Carmichael, D. B.: Fatal Bacterial Endocarditis dueto Staphylococcus aureus. U. S. Armed Forces M. J. 4: 287, 1953.
2. Finland, M., and Haight, T.: Antibiotic Resistanceof Pathogenic Staphylococci. Arch. Int. Med. 91: 143, 1953.
3. Reiss, E., Pulaski, E., and Contreras, A.: New EnglandJ. Med. 246: 611, 1952.
4. Sherris, J. C., and Florey, M. E.: Relation of PenicillinSensitivity in Staphylococci to Clinical Manifestations of Infection. Lancet1:309, 1951.
5. McGuire, J. M., et al.: "Ilotycine," a New Antibiotic.Antibiot. & Chemother. 2: 281, 1952.
6. Heilman, F. R., et al.: Some Laboratory andClinical Observations on a New Antibiotic, Erythromycin (Ilotycin). Proc.Staff Meet., Mayo Clin. 27: 285, 1952.
