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TRIMETHOPRIM-SULFAMETHOXAZOLE INDUCED RECURRENT ASEPTIC MENINGITIS
0022-5347/00/1645-1664/0 THE JOURNAL OF UROLOGY® Copyright © 2000 by AMERICAN UROLOGICAL ASSOCIATION, INC.®
Vol. 164, 1664 –1665, November 2000 Printed in U.S.A.
TRIMETHOPRIM-SULFAMETHOXAZOLE INDUCED RECURRENT ASEPTIC MENINGITIS MAXWELL V. MENG
AND
MARK ST. LEZIN
From the Departments of Urology, University of California San Francisco School of Medicine, San Francisco and Kaiser Permanente Hospital, Oakland, California KEY WORDS: antibiotics, trimethoprim-sulfamethoxazole combination, meningitis, urinary tract infections
Antibiotic use is widespread in daily urological practice. Complications of therapy, such as gastrointestinal upset, diarrhea, skin rash and hypersensitivity reactions, are common and readily recognized. However, rare side effects may not be so easily identified. We report a case of recurrent episodes of aseptic meningitis secondary to use of trimethoprim and sulfamethoxazole for urinary tract infection, and underscore the importance of recognizing this condition.
were initiated for presumed bacterial meningitis and the patient improved within a day of hospitalization. Bacterial, fungal and viral cultures and antigen tests from cerebrospinal fluid were negative. One year later the patient was treated with trimethoprim-sulfamethoxazole for irritative voiding symptoms. After 1 dose the patient was hospitalized for presumed urosepsis (episode 3). He improved during a 24-hour period and was prescribed nitrofurantoin for 10 days after hospital discharge.
CASE REPORT
A 74-year-old man presented with urinary frequency, urgency and dysuria 3.5 years after radical prostatectomy. He had recently been treated with ciprofloxacin for a presumed urinary tract infection. Because of several urinary tract infections during the last 2 years, further evaluation was pursued. History and physical examination were unremarkable. Prostate specific antigen was less than 0.2 ng./ml. Flexible cystoscopy did not reveal urethral stricture, bladder neck contracture or bladder stones. The patient received a single dose of 160 mg. trimethoprim and 800 mg. sulfamethoxazole after the procedure. He was hospitalized 6 hours later for presumed urosepsis. Clinical and laboratory data are shown in the table (episode 4). Trimethoprim-sulfamethoxazole was discontinued, and parenteral ampicillin and gentamicin were started. The patient improved rapidly the next day, even with discontinuation of antibiotics. On careful review of the medical record the patient had 3 prior episodes with similar characteristics. He was treated empirically with trimethoprim-sulfamethoxazole for a urinary tract infection 2 years after surgery. After a single oral dose, he was hospitalized for presumed urosepsis (episode 1). He improved rapidly on ampicillin and gentamicin, and was prescribed nitrofurantoin when discharged from the hospital. The antibiotic was changed to trimethoprim-sulfamethoxazole 5 days later when urine cultures yielded Escherichia coli. He returned after 1 dose (episode 2). Ampicillin and ceftriaxone Accepted for publication June 16, 2000.
DISCUSSION
Drug-induced aseptic meningitis has been associated with several groups of drugs and remains a diagnostic and therapeutic challenge. Multiple reports have documented many antimicrobials, such as trimethoprim-sulfamethoxazole, ciprofloxacin, cephalexin, metronidazole and isoniazid as causes of aseptic meningitis.1–3 Unless a high index of suspicion is maintained, aseptic meningitis may mimic an infectious process and, thus, remain unrecognized. Our patient had multiple episodes of aseptic meningitis due to trimethoprim-sulfamethoxazole use. The signs and symptoms of drug-induced meningitis include fever, headache, meningismus, nausea and vomiting, along with abnormal consciousness. This clinical constellation is nonspecific and urosepsis may seem more likely in the patient who has been prescribed an antibiotic for a urinary tract infection. The cerebrospinal fluid demonstrates a neutrophilic pleocytosis, normal to low glucose value, increased protein value and negative cultures. In our patient the close temporal relationship with the drug intake, absence of other explanations for the meningitis, cerebrospinal fluid findings and rapid resolution with trimethoprim-sulfamethoxazole cessation signaled druginduced aseptic meningitis. However, the diagnosis only became apparent with episode 4. Recurrent drug-induced aseptic meningitis has been reported in only 29 patients, the majority of
Clinical and laboratory findings after trimethoprim-sulfamethoxazole ingestion Episode 1 Latency (hrs.) Symptoms White blood cells (⫻109/l.) Urinalysis
3 Fever (103F), chills, malaise 9 Greater than 100 white blood cells/ high power field E. coli* – –
Urine culture Blood culture Cerebrospinal fluid: White blood count (cells/mm.3) % Neutrophils/%lymphocytes/%monocytes Protein (mg./dl.) Glucose (mg./dl.) Gram stain Culture * Sensitive to trimethoprim-sulfamethoxazole.
Episode 2
Episode 3
Episode 4
5 Fever (102F), chills, malaise, headache 13 Neg.
5 Fever (102F), chills, nausea/ anorexia, confusion 10 Greater than 100 white blood cells/high power field
6 Fever (104F), chills, malaise, meningismus 9 Neg.
Neg. Neg.
E. coli* Neg. –
Neg. Neg.
330
54
87/4/9
90/5/5
247 58 Neg. Neg.
110 66 Neg. Neg.
1664
TRIMETHOPRIM-SULFAMETHOXAZOLE INDUCED RECURRENT ASEPTIC MENINGITIS 1
which were associated with antibiotics. Treatment includes discontinuation of the offending drug and a search for potential etiology of the meningitis. Patients should be treated with a third generation cephalosporin if bacterial meningitis remains a possibility. Full recovery without sequela is typical. Our case illustrates a potential complication of antibiotics commonly used in urology, and stresses the importance of a thorough drug history and clinical awareness of an entity that is likely under diagnosed.
1665
REFERENCES
1. Moris, G. and Garcia-Monco, J. C.: The challenge of druginduced aseptic meningitis. Arch Intern Med, 159: 1185, 1999 2. Tunkel, A. R. and Starr, K.: Trimethoprim-sulfamethoxazoleassociated aseptic meningitis. Am J Med, 88: 696, 1990 3. Joffe, A. M., Farley, J. D., Linden, D. et al.: Trimethoprimsulfamethoxazole-associated aseptic meningitis: case reports and review of the literature. Am J Med, 87: 332, 1989
Vol. 164, 1664 –1665, November 2000 Printed in U.S.A.
TRIMETHOPRIM-SULFAMETHOXAZOLE INDUCED RECURRENT ASEPTIC MENINGITIS MAXWELL V. MENG
AND
MARK ST. LEZIN
From the Departments of Urology, University of California San Francisco School of Medicine, San Francisco and Kaiser Permanente Hospital, Oakland, California KEY WORDS: antibiotics, trimethoprim-sulfamethoxazole combination, meningitis, urinary tract infections
Antibiotic use is widespread in daily urological practice. Complications of therapy, such as gastrointestinal upset, diarrhea, skin rash and hypersensitivity reactions, are common and readily recognized. However, rare side effects may not be so easily identified. We report a case of recurrent episodes of aseptic meningitis secondary to use of trimethoprim and sulfamethoxazole for urinary tract infection, and underscore the importance of recognizing this condition.
were initiated for presumed bacterial meningitis and the patient improved within a day of hospitalization. Bacterial, fungal and viral cultures and antigen tests from cerebrospinal fluid were negative. One year later the patient was treated with trimethoprim-sulfamethoxazole for irritative voiding symptoms. After 1 dose the patient was hospitalized for presumed urosepsis (episode 3). He improved during a 24-hour period and was prescribed nitrofurantoin for 10 days after hospital discharge.
CASE REPORT
A 74-year-old man presented with urinary frequency, urgency and dysuria 3.5 years after radical prostatectomy. He had recently been treated with ciprofloxacin for a presumed urinary tract infection. Because of several urinary tract infections during the last 2 years, further evaluation was pursued. History and physical examination were unremarkable. Prostate specific antigen was less than 0.2 ng./ml. Flexible cystoscopy did not reveal urethral stricture, bladder neck contracture or bladder stones. The patient received a single dose of 160 mg. trimethoprim and 800 mg. sulfamethoxazole after the procedure. He was hospitalized 6 hours later for presumed urosepsis. Clinical and laboratory data are shown in the table (episode 4). Trimethoprim-sulfamethoxazole was discontinued, and parenteral ampicillin and gentamicin were started. The patient improved rapidly the next day, even with discontinuation of antibiotics. On careful review of the medical record the patient had 3 prior episodes with similar characteristics. He was treated empirically with trimethoprim-sulfamethoxazole for a urinary tract infection 2 years after surgery. After a single oral dose, he was hospitalized for presumed urosepsis (episode 1). He improved rapidly on ampicillin and gentamicin, and was prescribed nitrofurantoin when discharged from the hospital. The antibiotic was changed to trimethoprim-sulfamethoxazole 5 days later when urine cultures yielded Escherichia coli. He returned after 1 dose (episode 2). Ampicillin and ceftriaxone Accepted for publication June 16, 2000.
DISCUSSION
Drug-induced aseptic meningitis has been associated with several groups of drugs and remains a diagnostic and therapeutic challenge. Multiple reports have documented many antimicrobials, such as trimethoprim-sulfamethoxazole, ciprofloxacin, cephalexin, metronidazole and isoniazid as causes of aseptic meningitis.1–3 Unless a high index of suspicion is maintained, aseptic meningitis may mimic an infectious process and, thus, remain unrecognized. Our patient had multiple episodes of aseptic meningitis due to trimethoprim-sulfamethoxazole use. The signs and symptoms of drug-induced meningitis include fever, headache, meningismus, nausea and vomiting, along with abnormal consciousness. This clinical constellation is nonspecific and urosepsis may seem more likely in the patient who has been prescribed an antibiotic for a urinary tract infection. The cerebrospinal fluid demonstrates a neutrophilic pleocytosis, normal to low glucose value, increased protein value and negative cultures. In our patient the close temporal relationship with the drug intake, absence of other explanations for the meningitis, cerebrospinal fluid findings and rapid resolution with trimethoprim-sulfamethoxazole cessation signaled druginduced aseptic meningitis. However, the diagnosis only became apparent with episode 4. Recurrent drug-induced aseptic meningitis has been reported in only 29 patients, the majority of
Clinical and laboratory findings after trimethoprim-sulfamethoxazole ingestion Episode 1 Latency (hrs.) Symptoms White blood cells (⫻109/l.) Urinalysis
3 Fever (103F), chills, malaise 9 Greater than 100 white blood cells/ high power field E. coli* – –
Urine culture Blood culture Cerebrospinal fluid: White blood count (cells/mm.3) % Neutrophils/%lymphocytes/%monocytes Protein (mg./dl.) Glucose (mg./dl.) Gram stain Culture * Sensitive to trimethoprim-sulfamethoxazole.
Episode 2
Episode 3
Episode 4
5 Fever (102F), chills, malaise, headache 13 Neg.
5 Fever (102F), chills, nausea/ anorexia, confusion 10 Greater than 100 white blood cells/high power field
6 Fever (104F), chills, malaise, meningismus 9 Neg.
Neg. Neg.
E. coli* Neg. –
Neg. Neg.
330
54
87/4/9
90/5/5
247 58 Neg. Neg.
110 66 Neg. Neg.
1664
TRIMETHOPRIM-SULFAMETHOXAZOLE INDUCED RECURRENT ASEPTIC MENINGITIS 1
which were associated with antibiotics. Treatment includes discontinuation of the offending drug and a search for potential etiology of the meningitis. Patients should be treated with a third generation cephalosporin if bacterial meningitis remains a possibility. Full recovery without sequela is typical. Our case illustrates a potential complication of antibiotics commonly used in urology, and stresses the importance of a thorough drug history and clinical awareness of an entity that is likely under diagnosed.
1665
REFERENCES
1. Moris, G. and Garcia-Monco, J. C.: The challenge of druginduced aseptic meningitis. Arch Intern Med, 159: 1185, 1999 2. Tunkel, A. R. and Starr, K.: Trimethoprim-sulfamethoxazoleassociated aseptic meningitis. Am J Med, 88: 696, 1990 3. Joffe, A. M., Farley, J. D., Linden, D. et al.: Trimethoprimsulfamethoxazole-associated aseptic meningitis: case reports and review of the literature. Am J Med, 87: 332, 1989