Correspondence
(Iatelel transfusion
_ 6
____'____~
4
____'_________'__ 8 10
___L____L_
___L_____'______..J
12
16
14
18
20
Weeksfromtimeof initiation of Clarithromycin
While hematologic abnormalities are frequent in human immunodeficiency virus-infected patients with severe immunosuppression, profound reversible thrombocytopenia seems to be temporally related to clarithromycin therapy in this case. The mechanisms by which thrombocytopenia is mediated are unclear but appear to be related to suppression of platelet production. Peripheral destruction of platelets seems unlikely since the patient's platelet count increased after transfusion of random donor platelets. Thrombocytopenia induced by clarithromycin was reversible after therapy was stopped, but the long half-life of the drug may have contributed to the slow recovery of the bone marrow. It is unclear whether prior chemotherapy or extensive bone marrow replacement in association with disseminated MAC infection explains this patient's atypical response. However, we anxiously await the results of more clinical experience with this drug for determining whether our findings are collaborated by other researchers.
Figure 1. Platelet count during therapy with c1arithromycin.
Timothy A. Price and Carmelita U. Tuazon creased to 35,000/mm 3 (figure 1). At 6 weeks of therapy, all the patient's medications (zidovudine, clofazirnine, and amikacin) were discontinued, with the exception of clarithromycin and pentamidine (for prophylaxis). The dosage of clarithromycin was reduced to 1,000 mg/d. His platelet count remained --25,000/mm 3 for the next 6 weeks. Therapy with clarithromycin was discontinued when the platelet count further decreased to 17,000/mm 3 . When all medications were discontinued, the count increased to J5,000/mm 3 after I week. Two weeks after discontinuing therapy with clarithromycin, the patient received 6 units of random donor platelets for an unrelated diagnostic procedure. His platelet count was 68,000/mm 3 48 hours after transfusion. Eighteen days after the discontinuation of clarithromycin, a marked increase in the platelet count (to 100,000/mm 3) was noted. The platelet count remained at -- I 00,000/mm 3 on several determinations until his death 2 weeks later of acute respiratory failure. A request for an autopsy was denied.
Aseptic Meningitis Following Administration of Intravenous Immune Globulin SIR-We report a case of aseptic meningitis associated with the administration of intravenous immune globulin, a very unusual adverse reaction to this therapy. A 44-year-old woman with chronic idiopathic thrombocytopenic purpura was admitted to the hospital on 9 October 1991 for intravenous infusion with immune globulin before laser surgery for hemorrhagic uterine polyps. She underwent splenec-
Correspondence: Dr. Jean-Michel Molina. Infectious Diseases Unit. Hopital Saint-Louis. I Avenue C. Vellefaux, 75010. Paris, France. Clinical Infectious Diseases 1992;15:564-5 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1503-0036$02.00
Division of Infectious Diseases. Department of Medicine. The George Washington University Medical Center. Washington. D.C. References I. Fernandes PB. Hardy DJ. McDaniel D. Hanson CWo Swanson RN. In vitro and in vivo activities of darithromycin against Mycobacterium avium. Antimicrob Agents Chemother 1989;33: 1531-4. 2. Dautzenberg B. Trutfot C Legris S. et al. Activity of c1arithromycin against Mycobacterium Ql'iUIlI infection in patients with the acquired immune deficiency syndrome, a controlled clinical trial. Am Rev Respir Dis 1991;144:564-9. 3. Anderson G. Esmonde TS. Coles S. Macklin J. Carnegie C. A comparative safety and efficacy study ofcIarithromycin and erythromycin stearate in community-acquired pneumonia. J Antimicrob Chemother 1991;27(suppl A): I 17-24. 4. Poirier R. Comparative study ofclarithromycin and roxithromycin in the treatment of community-acquired pneumonia. J Antimicrob Chemother 1991;27(suppl A):I09-16. 5. Groopman JE. Zidovudine intolerance. Rev Infect Dis 1990;12(suppl 5):S500-6.
tomy 10years before admission and received pneumococcal vaccination. Remission, however, was short-lived, and she required therapy with prednisone (30 mg/d) to maintain a platelet count of --20 X 109/L. Eleven months before admission, she received a 3-day infusion of immune globulin (Venoglobulin, Alpha Therapeutics) at another hospital and experienced headache, chills, and vomiting. She was given 40 g (0.6 g/[kg· dD of intravenous immune globulin per day (Garnmagard, Baxter Healthcare) for 2 days. Onehour after completion of this therapy, which was given over a 4-hour period the second day, she experienced severe headache, vomiting, and fever. She was admitted again to the hospitalon II October 1991. Her temperature was 39.3°C, and she had marked neck stiffness and photophobia. A diagnosis ofbacterial meningitis or meningeal bleeding was considered. The white blood cell (WBC) count was 21 X 109/L, with 92% segmented neutrophils. The platelet count was 113 X 109/L.
Downloaded from http://cid.oxfordjournals.org/ at Monash University on June 16, 2015
O'---'------'_----'--------'_----'-------'_ -10 -8 -6 -4 -2 0 2
CID 1992; 15 (September)
CIO 1992; 15 (September)
Correspondence
565
associated with aseptic meningitis. The short duration of the second-day infusion for our patient might be one explanation for the development of aseptic meningitis. The clinical course of our patient is very similar to two previously reported cases of aseptic meningitis following intravenous immune globulin [3, 4]. All three cases have been of patients who had idiopathic thrombocytopenic purpura treated with steroids. Whether this is a mere coincidence is not known. We think, however, that aseptic meningitis should be added to the list ofadverse reactions following intravenous immune globulin infusions. This is potentially important since further infusion of immune globulin may induce a relapse of aseptic meningitis [1, 2].
Community-Acquired Bacteremia Due to Multiresistant Enterobacter in a Patient with Urosepsis
erythromycin. There was no previous hospitalization or institutionalization. She was febrile on admission, and there was no evidence of flank tenderness or back pain. The pelvic examination revealed no cystocele or vaginitis, and physical examination was otherwise unremarkable. Initial laboratory values revealed leukocytosis as well as a 2hour postprandial glucose level of 326 JLg/dL, BUN, 15 mg/dL, creatinine, 1.1 mgldL, and bicarbonate, 20.6 mEq/L. The urine was cloudy and yellow with a specific gravity of 1.023 and a pH of 5.0. Other laboratory findings were 2-5 white blood cells per high-power field, 2+ proteinuria, and a small amount of ketones. There was no hematuria. Urine, blood, and sputum specimens were submitted for gram staining and culture before the institution of antibiotics. The urine culture showed> 105 cfu of Enterobacter aerogenes per milliliter and 50,000 cfu of Proteus mirabilis per milliliter. Organisms were identified with use of the API20E strip (Analytab, Plainview, NY). Disk-diffusion and broth-microdilution susceptibility tests were performed according to standards set by the National Committee for Clinical Laboratory Standards (NeCLS) [6]. The broth-microdilution tests were performed with use ofSensititre plates (Radiometer, West Lake, OH). The findings were as follows (MICs are in parentheses): E. aerogenes was resistant to ampicillin (>32 J,Lg/mL), cefuroxime, ceftazidime (32 J,Lg/mL), arnpicillin/sulbactam (32/32 J,Lg/mL), and aztreonam (16 JLg/mL); intermediately resistant to ceftriaxone (16
SIR-Enterobacter are prominent nosocomial pathogens [1]. Third-generation cephalosporins may select for mutants that constitutively produce chromosomally mediated IJ-Iactamase [2-5). Multiresistant Enterobacter are becoming increasingly common in the nosocomial setting, but such organisms are thought to be rare in the community. We report an unusual occurrence of bacteremia due to multiresistant Enterobacter acquired from the community. A 74-year-old woman living at home who had no significant medical history and who was active and healthy until September 1991 presented with a progressive productive cough. Despite having received a 10-day course of erythromycin, she had dyspnea, fever (temperature to 102°F) with chills, and dysuria. She thought she had "passed a stone" 20 years ago but did not see a physician then. She had taken no antibiotics in recent memory and, specifically, none within the past 12 months except for
Correspondence: Dr. Jan Evans Patterson, Department of Medicine and Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street. New Haven. Connecticut 06510.
Clinical Infectious Diseases 1992;15:565-6 © 1992 by The University of Chicago. All rights reserved.
1058-4838/92/1503-0037$02.00
Jean-Michel Molina, Anne Coffineau, Jean-Didier Rain, DanielLetonturier, and Jacques Modal Infectious Diseases Unit and Hematology Section, Saint-Louis Hospital, Paris, France
References I. Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med 1991 ;325: 110-7. 2. Berkman SA, Lee ML. Gale RP. Clinical uses of intravenous immunoglobulins. Ann Intern Med 1990; 112:278-92. 3. Kato E, Shindo S, Eto Y, et al. Administration of immune globulin associated with aseptic meningitis. JAMA 1988;259:3269-71. 4. Casteels-Van Daele M, Wijndaele L. Hunninck K. Intravenous immune globulin and acute aseptic meningitis. N Engl J Med 1990;323:614-5.
Downloaded from http://cid.oxfordjournals.org/ at Monash University on June 16, 2015
Findings ofa computed tomographic scan of the head were normal. The CSF was clear and contained 1,830 X 106 WBCs/L with 83% neutrophils: 170 red blood cells/L: 1.38 g of protein per liter; and a normal glucose content. No pathogenic organisms were found in gram-stained preparations, and no antigens for pneumococci, meningococci, and Haemophilus injfuenzae were detected. Treatment with intravenous ceftriaxone ( 12 g/d) was initiated. Bacterial and fungal cultures of the CSF remained negative. Blood cultures were sterile. All symptoms subsided within 24 hours, and the patient was then referred to our unit. She was afebrile with only a mild headache. A second spinal tap was performed (4 days after the first one), and analysis of CSF showed 66 WBCs (with 91%lymphocytes), 0.64 g of protein per liter, and a normal glucose content. Results of tests for antinuclear antibodies were negative. Administration of antibiotics was discontinued, and the patient completely recovered. Our patient developed acute aseptic meningitis immediately following intravenous infusion of immune globulin. Intravenous immune globulin treatment has been reported to cause abdominal pain, headache, vomiting, and fever in some patients, but true meningitis has not been reported [I, 2]. These reactions occur at the end of the infusion period and last for several hours. Their mechanism is unknown, but they can be prevented by slowing the rate of the infusion or by pretreatment with corticosteroids [1,2]. We think the aseptic meningitis observed in this case might have been a major adverse reaction to intravenous immune globulin infusion. Our patient did not receive any antibiotic or antiinflammatory agents that have been
(Iatelel transfusion
_ 6
____'____~
4
____'_________'__ 8 10
___L____L_
___L_____'______..J
12
16
14
18
20
Weeksfromtimeof initiation of Clarithromycin
While hematologic abnormalities are frequent in human immunodeficiency virus-infected patients with severe immunosuppression, profound reversible thrombocytopenia seems to be temporally related to clarithromycin therapy in this case. The mechanisms by which thrombocytopenia is mediated are unclear but appear to be related to suppression of platelet production. Peripheral destruction of platelets seems unlikely since the patient's platelet count increased after transfusion of random donor platelets. Thrombocytopenia induced by clarithromycin was reversible after therapy was stopped, but the long half-life of the drug may have contributed to the slow recovery of the bone marrow. It is unclear whether prior chemotherapy or extensive bone marrow replacement in association with disseminated MAC infection explains this patient's atypical response. However, we anxiously await the results of more clinical experience with this drug for determining whether our findings are collaborated by other researchers.
Figure 1. Platelet count during therapy with c1arithromycin.
Timothy A. Price and Carmelita U. Tuazon creased to 35,000/mm 3 (figure 1). At 6 weeks of therapy, all the patient's medications (zidovudine, clofazirnine, and amikacin) were discontinued, with the exception of clarithromycin and pentamidine (for prophylaxis). The dosage of clarithromycin was reduced to 1,000 mg/d. His platelet count remained --25,000/mm 3 for the next 6 weeks. Therapy with clarithromycin was discontinued when the platelet count further decreased to 17,000/mm 3 . When all medications were discontinued, the count increased to J5,000/mm 3 after I week. Two weeks after discontinuing therapy with clarithromycin, the patient received 6 units of random donor platelets for an unrelated diagnostic procedure. His platelet count was 68,000/mm 3 48 hours after transfusion. Eighteen days after the discontinuation of clarithromycin, a marked increase in the platelet count (to 100,000/mm 3) was noted. The platelet count remained at -- I 00,000/mm 3 on several determinations until his death 2 weeks later of acute respiratory failure. A request for an autopsy was denied.
Aseptic Meningitis Following Administration of Intravenous Immune Globulin SIR-We report a case of aseptic meningitis associated with the administration of intravenous immune globulin, a very unusual adverse reaction to this therapy. A 44-year-old woman with chronic idiopathic thrombocytopenic purpura was admitted to the hospital on 9 October 1991 for intravenous infusion with immune globulin before laser surgery for hemorrhagic uterine polyps. She underwent splenec-
Correspondence: Dr. Jean-Michel Molina. Infectious Diseases Unit. Hopital Saint-Louis. I Avenue C. Vellefaux, 75010. Paris, France. Clinical Infectious Diseases 1992;15:564-5 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1503-0036$02.00
Division of Infectious Diseases. Department of Medicine. The George Washington University Medical Center. Washington. D.C. References I. Fernandes PB. Hardy DJ. McDaniel D. Hanson CWo Swanson RN. In vitro and in vivo activities of darithromycin against Mycobacterium avium. Antimicrob Agents Chemother 1989;33: 1531-4. 2. Dautzenberg B. Trutfot C Legris S. et al. Activity of c1arithromycin against Mycobacterium Ql'iUIlI infection in patients with the acquired immune deficiency syndrome, a controlled clinical trial. Am Rev Respir Dis 1991;144:564-9. 3. Anderson G. Esmonde TS. Coles S. Macklin J. Carnegie C. A comparative safety and efficacy study ofcIarithromycin and erythromycin stearate in community-acquired pneumonia. J Antimicrob Chemother 1991;27(suppl A): I 17-24. 4. Poirier R. Comparative study ofclarithromycin and roxithromycin in the treatment of community-acquired pneumonia. J Antimicrob Chemother 1991;27(suppl A):I09-16. 5. Groopman JE. Zidovudine intolerance. Rev Infect Dis 1990;12(suppl 5):S500-6.
tomy 10years before admission and received pneumococcal vaccination. Remission, however, was short-lived, and she required therapy with prednisone (30 mg/d) to maintain a platelet count of --20 X 109/L. Eleven months before admission, she received a 3-day infusion of immune globulin (Venoglobulin, Alpha Therapeutics) at another hospital and experienced headache, chills, and vomiting. She was given 40 g (0.6 g/[kg· dD of intravenous immune globulin per day (Garnmagard, Baxter Healthcare) for 2 days. Onehour after completion of this therapy, which was given over a 4-hour period the second day, she experienced severe headache, vomiting, and fever. She was admitted again to the hospitalon II October 1991. Her temperature was 39.3°C, and she had marked neck stiffness and photophobia. A diagnosis ofbacterial meningitis or meningeal bleeding was considered. The white blood cell (WBC) count was 21 X 109/L, with 92% segmented neutrophils. The platelet count was 113 X 109/L.
Downloaded from http://cid.oxfordjournals.org/ at Monash University on June 16, 2015
O'---'------'_----'--------'_----'-------'_ -10 -8 -6 -4 -2 0 2
CID 1992; 15 (September)
CIO 1992; 15 (September)
Correspondence
565
associated with aseptic meningitis. The short duration of the second-day infusion for our patient might be one explanation for the development of aseptic meningitis. The clinical course of our patient is very similar to two previously reported cases of aseptic meningitis following intravenous immune globulin [3, 4]. All three cases have been of patients who had idiopathic thrombocytopenic purpura treated with steroids. Whether this is a mere coincidence is not known. We think, however, that aseptic meningitis should be added to the list ofadverse reactions following intravenous immune globulin infusions. This is potentially important since further infusion of immune globulin may induce a relapse of aseptic meningitis [1, 2].
Community-Acquired Bacteremia Due to Multiresistant Enterobacter in a Patient with Urosepsis
erythromycin. There was no previous hospitalization or institutionalization. She was febrile on admission, and there was no evidence of flank tenderness or back pain. The pelvic examination revealed no cystocele or vaginitis, and physical examination was otherwise unremarkable. Initial laboratory values revealed leukocytosis as well as a 2hour postprandial glucose level of 326 JLg/dL, BUN, 15 mg/dL, creatinine, 1.1 mgldL, and bicarbonate, 20.6 mEq/L. The urine was cloudy and yellow with a specific gravity of 1.023 and a pH of 5.0. Other laboratory findings were 2-5 white blood cells per high-power field, 2+ proteinuria, and a small amount of ketones. There was no hematuria. Urine, blood, and sputum specimens were submitted for gram staining and culture before the institution of antibiotics. The urine culture showed> 105 cfu of Enterobacter aerogenes per milliliter and 50,000 cfu of Proteus mirabilis per milliliter. Organisms were identified with use of the API20E strip (Analytab, Plainview, NY). Disk-diffusion and broth-microdilution susceptibility tests were performed according to standards set by the National Committee for Clinical Laboratory Standards (NeCLS) [6]. The broth-microdilution tests were performed with use ofSensititre plates (Radiometer, West Lake, OH). The findings were as follows (MICs are in parentheses): E. aerogenes was resistant to ampicillin (>32 J,Lg/mL), cefuroxime, ceftazidime (32 J,Lg/mL), arnpicillin/sulbactam (32/32 J,Lg/mL), and aztreonam (16 JLg/mL); intermediately resistant to ceftriaxone (16
SIR-Enterobacter are prominent nosocomial pathogens [1]. Third-generation cephalosporins may select for mutants that constitutively produce chromosomally mediated IJ-Iactamase [2-5). Multiresistant Enterobacter are becoming increasingly common in the nosocomial setting, but such organisms are thought to be rare in the community. We report an unusual occurrence of bacteremia due to multiresistant Enterobacter acquired from the community. A 74-year-old woman living at home who had no significant medical history and who was active and healthy until September 1991 presented with a progressive productive cough. Despite having received a 10-day course of erythromycin, she had dyspnea, fever (temperature to 102°F) with chills, and dysuria. She thought she had "passed a stone" 20 years ago but did not see a physician then. She had taken no antibiotics in recent memory and, specifically, none within the past 12 months except for
Correspondence: Dr. Jan Evans Patterson, Department of Medicine and Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street. New Haven. Connecticut 06510.
Clinical Infectious Diseases 1992;15:565-6 © 1992 by The University of Chicago. All rights reserved.
1058-4838/92/1503-0037$02.00
Jean-Michel Molina, Anne Coffineau, Jean-Didier Rain, DanielLetonturier, and Jacques Modal Infectious Diseases Unit and Hematology Section, Saint-Louis Hospital, Paris, France
References I. Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med 1991 ;325: 110-7. 2. Berkman SA, Lee ML. Gale RP. Clinical uses of intravenous immunoglobulins. Ann Intern Med 1990; 112:278-92. 3. Kato E, Shindo S, Eto Y, et al. Administration of immune globulin associated with aseptic meningitis. JAMA 1988;259:3269-71. 4. Casteels-Van Daele M, Wijndaele L. Hunninck K. Intravenous immune globulin and acute aseptic meningitis. N Engl J Med 1990;323:614-5.
Downloaded from http://cid.oxfordjournals.org/ at Monash University on June 16, 2015
Findings ofa computed tomographic scan of the head were normal. The CSF was clear and contained 1,830 X 106 WBCs/L with 83% neutrophils: 170 red blood cells/L: 1.38 g of protein per liter; and a normal glucose content. No pathogenic organisms were found in gram-stained preparations, and no antigens for pneumococci, meningococci, and Haemophilus injfuenzae were detected. Treatment with intravenous ceftriaxone ( 12 g/d) was initiated. Bacterial and fungal cultures of the CSF remained negative. Blood cultures were sterile. All symptoms subsided within 24 hours, and the patient was then referred to our unit. She was afebrile with only a mild headache. A second spinal tap was performed (4 days after the first one), and analysis of CSF showed 66 WBCs (with 91%lymphocytes), 0.64 g of protein per liter, and a normal glucose content. Results of tests for antinuclear antibodies were negative. Administration of antibiotics was discontinued, and the patient completely recovered. Our patient developed acute aseptic meningitis immediately following intravenous infusion of immune globulin. Intravenous immune globulin treatment has been reported to cause abdominal pain, headache, vomiting, and fever in some patients, but true meningitis has not been reported [I, 2]. These reactions occur at the end of the infusion period and last for several hours. Their mechanism is unknown, but they can be prevented by slowing the rate of the infusion or by pretreatment with corticosteroids [1,2]. We think the aseptic meningitis observed in this case might have been a major adverse reaction to intravenous immune globulin infusion. Our patient did not receive any antibiotic or antiinflammatory agents that have been
