BRIEF CLINICAL OBSERVATIONS ERIC V. GRANO WZTZ, M.D. WILLIAM R. DONALDSON, M.D. PAUL R. SK~LNZK, M.D.

New England Medical Center Hospitals and Tufts University School of Medicine Boston, Massachusetts 1. Tilghman RC, Finland M. Clinical significance of bacteremia in pneumococcic pneumonia. Arch Intern Med 1937; 59: 602-19. 2. Burke JP, Klein JO, Gezon HM. Finland M. Pneumococcal bacteremia. Am J Dis Child 1971; 121: 353-9. 3. Shapiro ED, Wald ER, Brozanski BA. Periorbital cellulitis and paranasal sinusitis: a reappraisal. Pediatr Infect Dis 1982; 1: 914. 4. Sathyavagiswaran L, Dickinson PCT, Dobkin J. Rare Streptococcuspneumor iae soft tissue abscess. NY State J Med 1987; 87: 574. 5. DiNubile MJ, Albornoz MA, Stumacher RJ, et al. Pneumococcal soft-tissue infections: possible association with connective tissue diseases. J Infect Dis

1991; 163: 897-900. 6. Altemeier WA, Fuller WD. Prevention

and treatment

of gas gangrene.

JAMA

1971; 217: 806-13. 7. Caplan ES, Kluge RM. Gas gangrene:

review

of 34 cases. Arch Intern Med

1976; 136: 788-91. Submitted

August 22, 1991, and accepted

in revised

form January

29, 1692

EFFECTIVETREATMENT OF CEREBRAL TOXOPLASMOSISWITH DOXYCYCLINE ToxopZasmago&ii is an important causeof infection in the immunodeficient patient. It is a common causeof intracerebral masslesionsin patients with acquired immunodeficiency syndrome (AIDS) [l-3]. Standard treatment is with pyrimethamine and sulfadiaxine; however, drug toxicity occurs commonly, leading to discontinuation of therapy and recurrenceof toxoplasmaencephalitis.Clindamycin, trimethoprim-sulfamethoxaxole, and spiramycin arealternative drugswith variable effectiveness [2-4]. Chang and coworkers [5] investigated the in vitro and in vivo effectsof doxycyclineon T. gondii infection and discovereddoxycycline to be effective in the treatment of toxoplasma infections in peritoneal macrophagesand mice. The median survival reportedby the Toxoplasma Encephalitis Study Group for AIDS patients with toxoplasmaencephalitis is 4 months after the initiation of antiprotozoal therapy [6]. We report a case of T. gondii infection treated effectively with pyrimethamine and doxycycline for 19 months before death in a patient with AIDS. A 54-year-oldman with hemophilia and human immunodeficiency virus type 1 (HIV-l) infection was admitted to this medical center in June 1989 with mental status changesand frontal headaches but without visual problems. He had been diagnosed seropositive for HIV-l 18 months prior to this admission.

A thoroughevaluationwas doneand multiple cerebral lesions consistent with toxoplasmosiswere found on a computed tomographic (CT) scanof his head. Treatment was begun with pyrimethamine, sulfadiazine, and dexamethasone;there was improvement in his mental status and he was subsequently dischargedto home. The patient wasreadmitted in July 1989for evaluation of fever and a maculopapular rash on his trunk. The sulfadiaxinewasdiscontinued and clindamycin begun,with resolution of the rash.He was then dischargedto home receivingclindamycin and pyrimethamine. The patient did well, with subsequent magnetic resonanceimaging (MRI) scans showingno further increasein the size of the cerebral lesions. In March 1990,he developedtoxic epidermal necrolysis attributed to clindamycin. The clindamytin wasdiscontinuedand doxycycline,100mg twice a day, was begun along with the pyrimethamine. SubsequentheadCT and MRI scansshowedreduction in the sizeof the intracerebrallesions.Despite this, the patient’s health continued to deteriorate, with death from unrelated causesoccurring in late January 1991, 19 months after the diagnosis of toxoplasma encephalitis. Patients with AIDS and toxoplasmaencephalitis are generallyunable to tolerate treatment with pyrimethamine and sulfadiazine due to their toxicity [3]. Pyrimethamine when used alone has not been efficacioussinceserum and cerebrospinalfluid levels of this drug can possibly be lessthan the minimum effective concentration [3]. Turett and coworkers[7] found a failure rate of 83%in their doxycycline treatment of toxoplasmaencephalitis in six AIDS patients. Pope-Pegramand associates[8] effectively treated two AIDS patients with doxycycline for toxoplasmaencephalitis. We believe that doxycycline should also be consideredas an alternate drug to treat toxoplasma encephalitis in view of the favorableresult that was seenin our patient. JOSEPH T. MORRIS, M.D. J. WILLIAM KELLY, M.D.

Brooke Army Medical Center Fort Sam Houston, Texas 1. Wong B, Gold J, Brown A. et al. Central-nervous-system toxoplasmosis in homosexual men and parenteral drug abusers. Ann Intern Med 1984; 100: 36-42. 2. Luff B, Brooks R, Conley F, McCabe RE, Remington JS. Toxoplasmicencephalitis in patients with acquired immune deficiency syndrome. JAMA 1984; 252: 913-7. 3. Luff BJ. Remington JS. Toxoplasmicencephalitis. J Infect Dis 1988; 157: l-6. 4. Rolston KV. Hoy J. Role of clindamycin in the treatment of central nervous system toxoplasmosis. Am J Med 1987; 83: 551-4. 5. Chang HR, Comte R, Pech’ere JC. In vitro and in vivoeffects of doxycycline on ToxopLasma gondii. Antimicrob Agents Chemother 1990; 34: 775-80. 6. Haverkos HW. Assessment of therapy for toxoplasma encephalitis. The TE Study Group. Am J Med 1987; 82: 907-14.

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BRIEF CLINICAL 099ERVAl’lONS 7. Turett G, Pierone G, Masci J. Nicholas P. Failure of doxycydine in the treatment of cerebral toxoplasmosis [abstract Th.B.4791. In: Program and Abstracts of the Sixth International Conference on AIDS (San Francisco). 1990. 8. Popa-Pegram L. Gathe J. Bohn B, Piot D. Stool E. Treatment of presumed central nervous system toxoplasmosis with doxycycline [abstract MB. 20271. In: Program and Abstracts of the Seventh International Conference on AIDS (Florence, Italy). 1991. Submitted

June 12, 1991. and accepted

in revised form September

21, 1991

ANGIOTENSINCONVERTINGENZYME INHIBITORSAND LITHIUM TOXICITY Lithium is commonly prescribedfor manic-depressive disorders,while the angiotensin-convertingenzyme inhibitors (CEI) are a widely used class of antihypertensive agents.Both have effects on kidney function and excretion. We report two casesof lithium toxicity that developedwhen a CEI was prescribedto patients receivinglong-term maintenancelithium therapy.Toxicity occurredin the setting of a reversible decreasein renal function. The developmentof such toxicity can be accountedfor by the known pharmacologiceffectsof theseagents. Patient 1. The patient was a 49-year-oldwoman with manic-depressivedisorder treated with lithium for 10 years. She was admitted when she was noted to have a lithium level of 3.7mmol/L (therapeutic = 0.6 to 1.3 mmol/L) and continuous involuntary tremors of all her extremities. Her pulsewas 108/min and her temperature was 37.9OC.The blood urea nitrogen level was 13.9 mmol/L (39 mg/dL), the serumcreatininelevel was 194mmol/L (2.2 mg/dL), and the estimated glomerular filtration rate (GFR) was 33 mL/min. Twenty-four days prior to admission, the patient was hypertensive and beganto receivetreatment with lisinopri16 mg daily. There wasno changein the dosageof lithium. On admission, emergent hemodialysis was performed becauseof neurologiccomplicationsandthe degree of lithium toxicity. Immediately after 4 hours of initial hemodialysis,the lithium level was 3.2 mmol/L. Immediately after 4 hours of the second hemodialysis,the lithium level was0.8mmol/L. Six days later, the blood urea nitrogen was 2.8 mmol/L (8 mg/dL), the serum creatinine was 97 mmol/L (1.1 mg/dL), and the estimated GFR was 63 mL/min. Patient 2. The patient wasa 53-year-oldwoman with manic-depressivedisorder treated with lithium for many years.She had stable monthly therapeutic lithium levelsrangingfrom 0.7mmol/L to 0.8 mmol/L (therapeutic = 0.6to 1.3mmol/L). Shewas admitted when her lithium level waselevatedto 1.9

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mmol/L. Her maintenancedoseof lithium was unchanged.Twenty-six days prior to admission, she beganto receivetreatment with enalapri15mg daily for hypertension. She was being treated over the longterm with levothyroxinesodium 0.125mg daily for hypothyroidism. For the 4 days prior to admission, the patient was reported to be confused, tremulous,and polyuric. In the emergencyroom she was lethargic, oriented to person only, and had slurred speechand a coarsetremor. Her pulse was 120/min,her blood pressurewas 8O/!Xmm Hg, and she had dry oral mucosa.The lithium level was 1.8 mmol/L. The sodium was 159mmol/L, potassium was 6.0 mmol/L, blood urea nitrogen was 23 mmol/L (66 mg/dL), and creatinine was 169 mmol/L (1.8 mg/dL). The calculated GFR was 40 mL/min. Both lithium and enalapril were discontinued and the patient washydrated to replaceher free water deficit of 5 liters. Two days later, her lithium level was 0.8 mmol/L. Within 8 days, her blood ureanitrogen was2.8mmol/L (8 mg/dL) and serumcreatininewas80mmol/L (0.9mg/dL) with a calculatedGFR of 82mL/min. Without lithium and enalapril treatment, shehad stablerenal function 2 months later. Comments. In both cases,the patients developed acute lithium toxicity 3 to 4 weeksafter beginning treatment with a long-acting CEI without any changein lithium dosage.During the time interval from initiation of the CEI, thesepatients developed volume depletion as a result of the pharmacologic interaction betweenthe lithium and the CEI. This caused a reversible decrease in renal function, which reducedthe excretion of lithium and caused toxicity. Long-term lithium usagecan causenephrogenic diabetesinsipidus [l] and polyuria [2]. Lithium also induces a natriuresis by decreasingsodium reabsorption in proximal and distal convolutedtubules [3]. However, most patients receiving long-term lithium therapy are not sodium- or water-depleted becauseincreasedoral intake provides compensation. Patients receiving long-term lithium therapy may be dependenton an intact thirst mechanismto maintain a euhydrated state. The CEI reducethe production of angiotensinII, which by increasingefferentarteriolar constriction, maintains the GFR during statesof decreasedrenal blood flow [4,5].AngiotensinII is alsoa potent stimulus to thirst and drinking behavior [6], and its inhibition may reducedrinking behavior [7]. Lithium excretion is dependenton the GFR [8]. Both CEI and lithium causea natriuresis and this enhancesthe tendency for volume depletion. The CEI eliminate the compensatoryability of the effer-

Effective treatment of cerebral toxoplasmosis with doxycycline.

BRIEF CLINICAL OBSERVATIONS ERIC V. GRANO WZTZ, M.D. WILLIAM R. DONALDSON, M.D. PAUL R. SK~LNZK, M.D. New England Medical Center Hospitals and Tufts...
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