__I_ __ _ _ _ __ B_w __ Refer to: Wyler DJ, Glickman MG, Brewin A: Persistent serratia bacteremia associated with drug abuse. West J Med 122: 70-73, Jan 1975
Persistent Serratia Bacteremia Associated with Drug Abuse DAVID J. WYLER, MD MORTON G. GLICKMAN, MD AUSTIN BREWIN, MD San Francisco
INFECTIONs resulting from illicit intravenous use of drugs, often with unusual pathogens and manner of presentation, are becoming increasingly common.' We report an unusual case of persistent bacteremia, caused by Serratia marcescens and complicated by the development of mycotic aneurysm, in a patient using methylphenidate hydrochloride (Ritalin®) intravenously. "Total body" arteriography identified the occult septic foci in this case of bacteremia that was refractory to aggressive antibiotic therapy.
Report of a Case A 47-year-old Causacian man entered the hospital after one week of symptoms, including dyspnea, arthralgias, myalgias, and hematuria. For five years, the patient had been injecting himself with nonsterile solutions of filtered, pulverized methylphenidate hydrochloride. He had had multiple episodes of fever, chills, and hematuria that had required admission to hospital. Acute glomerulonephritis of nonstreptococcal origin was diagnosed on at least one occasion; bacteremia was at no time documented. From the Departments of Medicine (Drs. Wyler and Brewin); and Radiology (Dr. Glickman), University of California, San Francisco, and the San Francisco General Hospital. Dr. Wyler is now with the Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Submitted, revised, June 24, 1974. Reprint requests to: Editorial Office, Room 994-M, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143.
70
JANUARY 1975 * 122 * 1
On admission, the patient appeared acutely ill. The blood pressure was 130/75 mm of mercury, the pulse was 100 per minute, and rectal temperature was 39°C (102.2°F). His skin had "needle tracks" without evidence of inflammation, and petechiae were noted on the left thigh. No splinter hemorrhages, Osler's nodes, Janeway's spots, or Roth's spots were present. There was bilateral costovertebral angle tenderness to percussion. The rest of the physical examination was entirely within normal limits. The hematocrit was 29 percent and leukocytes numbered 12,600 per cu mm with a normal differential count. Urinalysis showed isosthenuria and gross hematuria without cylindruria or proteinuria; serum electrolytes were normal except for moderate hyponatremia and hypochloremia. Blood urea nitrogen was 44 mg per 100 ml, serum creatinine was 2.9 mg per 100 ml, and creatinine clearance was 11 ml per minute. Roentgenograms of the chest and abdomen and an electrocardiogram were essentially normal. Six blood cultures were obtained, and the patient was given cephalothin (1 gram intravenously every six hours) and kanamycin (a single 1-gram dose intramuscularly) on an empirical basis. On the following day, all blood cultures yielded Serratia marcescens, which was sensitive to chloramphenicol, kanamycin, gentamicin, and carbenicillin. Urine cultures grew approximately 5,000 colonies of S. marcescens with the same spectrum of antibiotic sensitivities. Sputum cultures grew normal oral flora. Gentamicin (80 mg intramuscularly three time daily) and carbenicillin (a 30-gram loading dose followed by 5 grams intravenously twice daily) were administered, and cephalothin and kanamycin were discontinued. Dosages and schedule were altered in line with the results of serum bactericidal determinations and drug synergism studies, as well as the patient's changing renal function. On the second hospital day, petechiae in the conjunctiva of the left eye were noted for the first time. During the next 48 hours, pronounced chemosis developed, and full-blown endophthalmitis followed. Intraconjunctival injections of gentamicin and steroids arrested the local infec-
CASE REPORT
.~~~k .._"
..,
b
-
Figure 1.-Superior mesenteric artery Injection. Irregularity in the proximal portion of the superior mesenteric artery may represent arteriosclerosis. More distally, a discrete, lobulated aneurysm is opacified. Adjacent portion of the superior mesenteric artery and an ileal branch are narrowed in proximity to the aneurysm (arrows). Surrounding arterial narrowing, a sign of infection, suggests that this is a mycotic aneurysm.
tion but all vision was lost in that eye. Lumbar puncture and brain scan were negative. The patient's temperature became normal and remained so for one week. However, fever returned [38°C (100.4°F) rectally], and cultures of blood once more grew S. marcescens. An aggressive search for a septic focus, including roentgenograms of chest and bones and radioisotope scans of brain, lung, liver, and spleen, was unsuccessful. An intravenous pyelogram showed no focal defects. The left eye was enucleated, but it was not infected. Three weeks after admission, blood cultures remained positive for Serratia marcescens, which now showed stepwise resistance to the antibiotics used. Therefore, chloramphenicol (500 mg intramuscularly every four hours) was added to the regimen. Because of the failure to demonstrate by less invasive methods a focus of infection seeding the
circulating blood, multiple selective visceral arteriograms were performed, Aortic, iliac, carotid, vertebral, renal, and inferior mesenteric angiograms were normal, as was an inferior cavagram. A selective celiac angiogram, however, showed pooling of contrast medium in the liver, and selective study of the superior mesenteric artery demonstrated radiographic signs consistent with a mycotic aneurysm (Figures 1 and 2). Because there were no stigmata of endocarditis, cardiac murmurs, or septic pulmonary emboli, cardiac catheterization was not done. Neither resection nor drainage of the hepatic abscess was performed because the surgical approach to its precise location was felt to carry too great a risk. Since only surgical removal of both foci could contribute to eradication of the infection, it was decided not to attempt resection of the mycotic aneurysm, but rather to treat the patient medically. Fortunately, he became afebrile and cultures of the blood became sterile. Gentamicin was discontinued on the 59th hospital day and carbenicillin and chloramphenicol were stopped on the 66th day. The patient remained afebrile, with sterile blood cultures, and was doing well several months after discharge.
Discussion This case presents some unusual complications of bacteremia secondary to intravenous drug abuse. First, S. marcescens bacteremia without endocarditis is rarely seen in patients who abuse drugs, although endocarditis requiring surgical debridement has been reported in this setting.2-4 Second, metastatic bacterial endophthalmitis as a complication of addiction has not been noted in the literature, although fungal endophthalmitis has been reported.5 Third, the development of stepwise resistance to antibiotics in this strain of S. marcescens was a curious, worrisome observation. Finally, mycotic aneurysm and hepatic abscess, rarely seen in association with Serratia,8 7 were sources of persistent bacterial showering into the blood stream, and this accounted for continued bacteremia despite aggressive antibiotic therapy. After failure to locate the foci of infection by all noninvasive techniques, only laparotomy and angiography were available. Angiography was carried out and the sources of seeding were delineated thereby. Although simple aortography may be the best initial approach, this technique may not demonstrate an abscess or mycotic aneurysm since suboptimal opacification and superimTHE WESTERN JOURNAL OF MEDICINE
71
CASE REPORT
.'!
fs
Jo'S .
;S.:
4
Figure 2.-Common hepatic artery injection. A. Several vessels in midportion of the right lobe of the liver are arched and displaced around a 5-cm lesion (solid arrows). The mass is avascular except for a single artery (open arrow), which is straightened. It courses through or is superimposed on the lesion. B. In the parenchymal phase, an ovoid collection of contrast medium appears at the center of the mass. A slowly filling branch of the hepatic artery (arrow) communicates with the extravascular collection of contrast medium. C. Ten minutes after the common hepatic artery injection, persistent vague opacification of the extravascular collection is seen (arrows). The mass appears 3 mm larger than in the parenchymal phase, indicating that extravasation has occurred into a liquid through which the contrast medium can diffuse further toward the periphery. This strongly suggests an intrahepatic abscess, rather than mycotic aneurysm, in the liver.
72
JANUARY 1975 * 122 *
1
CASE REPORT
position of branch vessels reduce the diagnostic accuracy of the procedure (Figure 3). Therefore, selective angiography should be undertaken, beginning with the heart (when endocarditis is suspected) and abdominal viscera, because these organs are most likely to house the source of bacteremia. A mycotic aneurysm has many typical features (Figure 1); an abscess may be diagnosed by the particular vascular pattern it produces by displacement of vessels, by communication of an opacified vessel with a necrotic center, by defects in the parenchymal phase of the injection, or even by a hypervascular rim around the perimeter of the abscess (Figure 2). Injection of contrast medium into the celiac artery and, if possible, into the inferior phrenic artery allows a search for subphrenic, subhepatic, or peripancreatic abscesses. An inferior venacavagram is also useful, as mycotic aneurysms have occurred in this vessel. Examination of the extremities is more readily accomplished through clinical, thermographic, and ultrasonic methods. The more recent use of gallium scans may also prove useful in such clinical situations. Surgical resection is the treatment of choice if all aneurysms that are sources of bacteria can be eradicated. Therefore, preoperative "total body" angiography is indicated. Surgical operation was contraindicated in our patient because of the unfavorable location of the hepatic abscess. It was surprising and gratifying that the foci of infection were rendered sterile by long-term antibiotic therapy alone. The morbidity of such extensive angiography is low,8 9 and such as does occur is probably related to the catheterization time and total volume of contrast medium infused. Therefore, this procedure should be undertaken in two or three stages, on separate days and preferably when the patient is clinically stable. Our experience with this patient, who had unusual complications of illicit intravenous injection of a drug, points out that angiography can be a highly effective, relatively benign method of locating foci of infection after less invasive techniques have failed. While surgical resection is the treatment of choice, occasionally these foci can be eradicated by antibiotic therapy alone when operation is contraindicated.
Summary Bacteremia caused by Serratia marcescens developed in a patient who was injecting pulverized
*V
..
Y:s'
Figure 3.-Abdominal aortogram. Although all major branches of the aorta are opacified, neither the aneurysm in the mesenteric artery nor the hepatic abscess is opacified.
methylphenidate hydrochloride (Ritalin®). Metastatic endophthalmitis, mycotic aneurysm, and hepatic abscess developed as complications of the infection. After initially successful treatment, recurrent bacteremia heralded the presence of occult foci of infection. "Total body" selective angiography then located these foci after other diagnostic techniques had failed. REFERENCES 1. Cherubin CE: Infectious disease problems of narcotic addicts. Arch Intern Med 128:309-313, 1971 2. Alexander R, Holloway GA Jr, Honsinger RW Jr: Surgical debridement for resistant bacterial endocarditis-A case of antibiotic-refractory Serratia marcescens infection on the tricuspid valve cured by operative excision. JAMA 210:1757-1759, 1969 3. Quintiliani R, Gifford RH: Endocarditis from Serratia marcescens. JAMA 208:2055-2059, 1969 4. Dodson WH: Serratia marcescens septicemia. Arch Intern Med 121:145-150, 1968 5. Sugar HS, Mandell GH, Shalev J: Metastic endophthalmitis associated with injection of addictive drugs. Am J Ophthalmol 71:1055-1058, 1971 6. Blum L, Keefer EBC: Clinical entity of cryptogenic mycotic aneurysm: Report of six cases. JAMA 188:505-508, 1964 7. Cliff MM, Soulen RL, Finestone AJ: Mycotic aneurysmsA challenge and a clue: Review of ten-year experience. Arch Intern Med 126:977-982, 1970 8. Amundsen P, Dietrichson P, Engle I, et al: Cerebral angiography by catheterization-Complications and side effects. Acta Radiol [Diagn] 1:164-172, 1963 9. Pollard JJ, Nebesar RA, Mattoso LF: Angiographic diagnosis of benign diseases of the liver. Radiology 86:276, 1966
THE WESTERN JOURNAL OF MEDICINE
73
Persistent Serratia Bacteremia Associated with Drug Abuse DAVID J. WYLER, MD MORTON G. GLICKMAN, MD AUSTIN BREWIN, MD San Francisco
INFECTIONs resulting from illicit intravenous use of drugs, often with unusual pathogens and manner of presentation, are becoming increasingly common.' We report an unusual case of persistent bacteremia, caused by Serratia marcescens and complicated by the development of mycotic aneurysm, in a patient using methylphenidate hydrochloride (Ritalin®) intravenously. "Total body" arteriography identified the occult septic foci in this case of bacteremia that was refractory to aggressive antibiotic therapy.
Report of a Case A 47-year-old Causacian man entered the hospital after one week of symptoms, including dyspnea, arthralgias, myalgias, and hematuria. For five years, the patient had been injecting himself with nonsterile solutions of filtered, pulverized methylphenidate hydrochloride. He had had multiple episodes of fever, chills, and hematuria that had required admission to hospital. Acute glomerulonephritis of nonstreptococcal origin was diagnosed on at least one occasion; bacteremia was at no time documented. From the Departments of Medicine (Drs. Wyler and Brewin); and Radiology (Dr. Glickman), University of California, San Francisco, and the San Francisco General Hospital. Dr. Wyler is now with the Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Submitted, revised, June 24, 1974. Reprint requests to: Editorial Office, Room 994-M, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143.
70
JANUARY 1975 * 122 * 1
On admission, the patient appeared acutely ill. The blood pressure was 130/75 mm of mercury, the pulse was 100 per minute, and rectal temperature was 39°C (102.2°F). His skin had "needle tracks" without evidence of inflammation, and petechiae were noted on the left thigh. No splinter hemorrhages, Osler's nodes, Janeway's spots, or Roth's spots were present. There was bilateral costovertebral angle tenderness to percussion. The rest of the physical examination was entirely within normal limits. The hematocrit was 29 percent and leukocytes numbered 12,600 per cu mm with a normal differential count. Urinalysis showed isosthenuria and gross hematuria without cylindruria or proteinuria; serum electrolytes were normal except for moderate hyponatremia and hypochloremia. Blood urea nitrogen was 44 mg per 100 ml, serum creatinine was 2.9 mg per 100 ml, and creatinine clearance was 11 ml per minute. Roentgenograms of the chest and abdomen and an electrocardiogram were essentially normal. Six blood cultures were obtained, and the patient was given cephalothin (1 gram intravenously every six hours) and kanamycin (a single 1-gram dose intramuscularly) on an empirical basis. On the following day, all blood cultures yielded Serratia marcescens, which was sensitive to chloramphenicol, kanamycin, gentamicin, and carbenicillin. Urine cultures grew approximately 5,000 colonies of S. marcescens with the same spectrum of antibiotic sensitivities. Sputum cultures grew normal oral flora. Gentamicin (80 mg intramuscularly three time daily) and carbenicillin (a 30-gram loading dose followed by 5 grams intravenously twice daily) were administered, and cephalothin and kanamycin were discontinued. Dosages and schedule were altered in line with the results of serum bactericidal determinations and drug synergism studies, as well as the patient's changing renal function. On the second hospital day, petechiae in the conjunctiva of the left eye were noted for the first time. During the next 48 hours, pronounced chemosis developed, and full-blown endophthalmitis followed. Intraconjunctival injections of gentamicin and steroids arrested the local infec-
CASE REPORT
.~~~k .._"
..,
b
-
Figure 1.-Superior mesenteric artery Injection. Irregularity in the proximal portion of the superior mesenteric artery may represent arteriosclerosis. More distally, a discrete, lobulated aneurysm is opacified. Adjacent portion of the superior mesenteric artery and an ileal branch are narrowed in proximity to the aneurysm (arrows). Surrounding arterial narrowing, a sign of infection, suggests that this is a mycotic aneurysm.
tion but all vision was lost in that eye. Lumbar puncture and brain scan were negative. The patient's temperature became normal and remained so for one week. However, fever returned [38°C (100.4°F) rectally], and cultures of blood once more grew S. marcescens. An aggressive search for a septic focus, including roentgenograms of chest and bones and radioisotope scans of brain, lung, liver, and spleen, was unsuccessful. An intravenous pyelogram showed no focal defects. The left eye was enucleated, but it was not infected. Three weeks after admission, blood cultures remained positive for Serratia marcescens, which now showed stepwise resistance to the antibiotics used. Therefore, chloramphenicol (500 mg intramuscularly every four hours) was added to the regimen. Because of the failure to demonstrate by less invasive methods a focus of infection seeding the
circulating blood, multiple selective visceral arteriograms were performed, Aortic, iliac, carotid, vertebral, renal, and inferior mesenteric angiograms were normal, as was an inferior cavagram. A selective celiac angiogram, however, showed pooling of contrast medium in the liver, and selective study of the superior mesenteric artery demonstrated radiographic signs consistent with a mycotic aneurysm (Figures 1 and 2). Because there were no stigmata of endocarditis, cardiac murmurs, or septic pulmonary emboli, cardiac catheterization was not done. Neither resection nor drainage of the hepatic abscess was performed because the surgical approach to its precise location was felt to carry too great a risk. Since only surgical removal of both foci could contribute to eradication of the infection, it was decided not to attempt resection of the mycotic aneurysm, but rather to treat the patient medically. Fortunately, he became afebrile and cultures of the blood became sterile. Gentamicin was discontinued on the 59th hospital day and carbenicillin and chloramphenicol were stopped on the 66th day. The patient remained afebrile, with sterile blood cultures, and was doing well several months after discharge.
Discussion This case presents some unusual complications of bacteremia secondary to intravenous drug abuse. First, S. marcescens bacteremia without endocarditis is rarely seen in patients who abuse drugs, although endocarditis requiring surgical debridement has been reported in this setting.2-4 Second, metastatic bacterial endophthalmitis as a complication of addiction has not been noted in the literature, although fungal endophthalmitis has been reported.5 Third, the development of stepwise resistance to antibiotics in this strain of S. marcescens was a curious, worrisome observation. Finally, mycotic aneurysm and hepatic abscess, rarely seen in association with Serratia,8 7 were sources of persistent bacterial showering into the blood stream, and this accounted for continued bacteremia despite aggressive antibiotic therapy. After failure to locate the foci of infection by all noninvasive techniques, only laparotomy and angiography were available. Angiography was carried out and the sources of seeding were delineated thereby. Although simple aortography may be the best initial approach, this technique may not demonstrate an abscess or mycotic aneurysm since suboptimal opacification and superimTHE WESTERN JOURNAL OF MEDICINE
71
CASE REPORT
.'!
fs
Jo'S .
;S.:
4
Figure 2.-Common hepatic artery injection. A. Several vessels in midportion of the right lobe of the liver are arched and displaced around a 5-cm lesion (solid arrows). The mass is avascular except for a single artery (open arrow), which is straightened. It courses through or is superimposed on the lesion. B. In the parenchymal phase, an ovoid collection of contrast medium appears at the center of the mass. A slowly filling branch of the hepatic artery (arrow) communicates with the extravascular collection of contrast medium. C. Ten minutes after the common hepatic artery injection, persistent vague opacification of the extravascular collection is seen (arrows). The mass appears 3 mm larger than in the parenchymal phase, indicating that extravasation has occurred into a liquid through which the contrast medium can diffuse further toward the periphery. This strongly suggests an intrahepatic abscess, rather than mycotic aneurysm, in the liver.
72
JANUARY 1975 * 122 *
1
CASE REPORT
position of branch vessels reduce the diagnostic accuracy of the procedure (Figure 3). Therefore, selective angiography should be undertaken, beginning with the heart (when endocarditis is suspected) and abdominal viscera, because these organs are most likely to house the source of bacteremia. A mycotic aneurysm has many typical features (Figure 1); an abscess may be diagnosed by the particular vascular pattern it produces by displacement of vessels, by communication of an opacified vessel with a necrotic center, by defects in the parenchymal phase of the injection, or even by a hypervascular rim around the perimeter of the abscess (Figure 2). Injection of contrast medium into the celiac artery and, if possible, into the inferior phrenic artery allows a search for subphrenic, subhepatic, or peripancreatic abscesses. An inferior venacavagram is also useful, as mycotic aneurysms have occurred in this vessel. Examination of the extremities is more readily accomplished through clinical, thermographic, and ultrasonic methods. The more recent use of gallium scans may also prove useful in such clinical situations. Surgical resection is the treatment of choice if all aneurysms that are sources of bacteria can be eradicated. Therefore, preoperative "total body" angiography is indicated. Surgical operation was contraindicated in our patient because of the unfavorable location of the hepatic abscess. It was surprising and gratifying that the foci of infection were rendered sterile by long-term antibiotic therapy alone. The morbidity of such extensive angiography is low,8 9 and such as does occur is probably related to the catheterization time and total volume of contrast medium infused. Therefore, this procedure should be undertaken in two or three stages, on separate days and preferably when the patient is clinically stable. Our experience with this patient, who had unusual complications of illicit intravenous injection of a drug, points out that angiography can be a highly effective, relatively benign method of locating foci of infection after less invasive techniques have failed. While surgical resection is the treatment of choice, occasionally these foci can be eradicated by antibiotic therapy alone when operation is contraindicated.
Summary Bacteremia caused by Serratia marcescens developed in a patient who was injecting pulverized
*V
..
Y:s'
Figure 3.-Abdominal aortogram. Although all major branches of the aorta are opacified, neither the aneurysm in the mesenteric artery nor the hepatic abscess is opacified.
methylphenidate hydrochloride (Ritalin®). Metastatic endophthalmitis, mycotic aneurysm, and hepatic abscess developed as complications of the infection. After initially successful treatment, recurrent bacteremia heralded the presence of occult foci of infection. "Total body" selective angiography then located these foci after other diagnostic techniques had failed. REFERENCES 1. Cherubin CE: Infectious disease problems of narcotic addicts. Arch Intern Med 128:309-313, 1971 2. Alexander R, Holloway GA Jr, Honsinger RW Jr: Surgical debridement for resistant bacterial endocarditis-A case of antibiotic-refractory Serratia marcescens infection on the tricuspid valve cured by operative excision. JAMA 210:1757-1759, 1969 3. Quintiliani R, Gifford RH: Endocarditis from Serratia marcescens. JAMA 208:2055-2059, 1969 4. Dodson WH: Serratia marcescens septicemia. Arch Intern Med 121:145-150, 1968 5. Sugar HS, Mandell GH, Shalev J: Metastic endophthalmitis associated with injection of addictive drugs. Am J Ophthalmol 71:1055-1058, 1971 6. Blum L, Keefer EBC: Clinical entity of cryptogenic mycotic aneurysm: Report of six cases. JAMA 188:505-508, 1964 7. Cliff MM, Soulen RL, Finestone AJ: Mycotic aneurysmsA challenge and a clue: Review of ten-year experience. Arch Intern Med 126:977-982, 1970 8. Amundsen P, Dietrichson P, Engle I, et al: Cerebral angiography by catheterization-Complications and side effects. Acta Radiol [Diagn] 1:164-172, 1963 9. Pollard JJ, Nebesar RA, Mattoso LF: Angiographic diagnosis of benign diseases of the liver. Radiology 86:276, 1966
THE WESTERN JOURNAL OF MEDICINE
73
