CORRESPONDENCE

COMBINATION THERAPY VERSUSMONOTHERAPYFOR PSEUDOMONASAERUGINOSA BACTEREMIA To the Editor:

In the recent article by Hilf et al (Am J Med 1989; 87: 540-6), the authors state that it is their contention that “combination therapy is superior to monotherapy.” They define combination therapy as simultaneous use of an antipseudomonal @-lactam agent plus an aminoglycoside. However, there is no definition of monotherapy. Specifically, how many of their patients receiving monotherapy had an aminoglycoside as the sole agent versus an antipseudomonal P-lactam? Were there any statistically significant differences in outcome between those patients receiving combination therapy and those receiving monotherapy with an antipseudomonal ,B-lactam, assuming there were enough patients for comparison? It would also be useful to know whether the authors considered delay in institution of therapy (combination or single agent) as a potential confounding variable in outcome and whether or not a minimal duration of treatment with any agent was considered necessary before inclusion in the analysis. JAMES E. BROSS, M.D. Geisinger Medical Center Danville, Pennsylvania Submitted

December

29, 1989, and accepted July 12, 1990

The Reply:

Of the 200 patients in the study, 14 received no antipseudomonal agent therapy, 143 received combination therapy consisting of a P-lactam agent and an aminoglycoside, 37 received an aminoglycoside alone, and only six received antipseudomonal @lactam monotherapy. As our article stated, the mor-

tality rate for the combination therapy was always lower than that for monotherapy (Table III in our article). When the analysis was confined to aminoglycoside therapy alone, the mortality rate for aminoglycoside monotherapy remained statistically significantly higher than that for combination therapy. The mortality rate for @-lactam monotherapy was also higher than that for combination therapy, but the small number of patients precluded valid statistical analysis; furthermore, none of the patients receiving /3-lactam monotherapy were classified as “critically ill” (Results section and Appendix), which favored a better outcome. We did analyze the patients with respect to delay in institution of appropriate therapy (combination or monotherapy). Interestingly, we found that those receiving antibiotics on the day of or prior to a positive blood culture actually did worse than those receiving antibiotics 1 or more days after a positive blood culture. The reason for this paradox was due to the fact that the patients receiving early administration were more likely to be critically ill. When the subgroup of patients who were judged to be critically ill was excluded from analysis, we found that delay of institution of therapy was comparabIe for both groups and was not the reason for the difference in mortality between those receiving combination therapy and those receiving monotherapy. Unless the patient died, all patients underwent antipseudomonal antibiotic therapy for at least 7 days.

NONTUBERCULOUS MYCOBACTERIAL RHEUMATISM-FACT OR FICTION? To the Editor:

I read the clinical observation by Maricic and Alepa (Am J Med 1990; 88: 549-50) with great interest. I entirely agree with their opinion that Mycobacterium avium-intracellulare (MAI) infection should be considered even in normal hosts without predisposing conditions, especially the elderly. In Japan also, the prevalence rate of nontuberculous mycobacterial infections including MA1 has been increasing, particularly since 1984, and the average age of a newly admitted patient with MAI infection is over 65 years [ 11. However, I would like to make several comments. First, Maricic and Alepa’s patient was diagnosed as having the first case of reactive arthritis after MAI infection. However, I suspect that direct MA1 infection of the synovium was important in the pathogenesis of the arthritis. The patient at first developed only monoarticular arthritis, although she later had joint swelling of the opposite site. Reactive arthritis associated with tuberculosis (i.e., Poncet’s disease or tuberculous rheumatism) is a sterile polyarthritis and not a monoarthritis [2]. Moreover, patients with other types of reactive arthritis such as Reiter’s syndrome and Lyme arthritis usually do not demonstrate monoarticular arthritis [3,4]. In contrast, all of Berney et al’s [5] 25 patients with tuberculous arthritis, which is characterized by direct tuberculous involvement, had a monoarthritis. Previously reported VICTOR L. Yu, M.D., F.A.C.P. patients with arthritis associated MEGAN HILF, MS. MAI infection also had monUniversity of Pittsburgh School of with oarthritis or bilateral symmetric Medicine arthritis 16-81. Pittsburgh, Pennsylvania January

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CORRESPONDENCE

Second, absence of MA1 in the affected joint of Maricic and Alepa’s patient was confirmed merely by synovial fluid culture. Although results of synovial fluid culture are positive in approximately 80% of cases of tuberculous arthritis [5,9], data on nontuberculous mycobacteriosis are not as abundant. A diagnosis of nontuberculous mycobacterial septic arthritis or periarthritis was eventually established in 39 of 46 cases (85%) by surgically excised tissue. In only 15% was a diagnosis made by culture of joint or bursal fluid [lo]. I agree with Messner [ll] that the quickest and the most reliable method of diagnosis of mycobacterial arthritis is biopsy. I think that we need to know whether results of biopsy and culture of synovial tissue were also negative in Maricic and Alepa’s patient. Apart from this, Borrelia burgdorferi-an offending microorganism of Lyme disease-has recently been demonstrated in the synovial fluid of a patient with Lyme arthritis [El. The possibility exists that MA1 might have been identified in the patient described by Maritic and Alepa. Third, the authors state that the patient was a normal host. However, I suspect that she had an underlying illness, namely another form of arthritis such as a connective tissue disease, because she had Raynaud’s phenomenon and livedo reticularis. Mycobacterial arthritis might coexist with rheumatoid arthritis and systemic lupus erythematosus [5,10]. Last, in agreement with Poncet, I would like to recommend the term “nontuberculous mycobacterial rheumatism” rather than “reactive arthritis after MA1 infection.” HIDETO

Keio University

School

AKAMA,

M.D.

of Medicine

Tokyo,

Japan

1. Tsukamura

M, Kita N, Shimoide H, et al. Studies on the nontuberculous lung mycobacteriosis in Japan (report of the study in the year 1986 of the

136

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Mycobacteriosis Research Group of the Japanese National Chest Hospitals)., [Abstract in English.] Kekkaku 1988; 63: 493-9. 2. lsaacs AJ. Sturrock RD. Poncet’s disease-fact or fiction? A re-appraisal of tuberculous rheumatism. Tubercle 1974; 55: 135-42. 3. Ford OK. Reiter’s syndrome: reactive arthritis. In: McCarty DJ, ed. Arthritis and allied conditions. 11th ed. Philadelphia: Lea & Febiger, 1989: 944-53. 4. Kolstoe J, Messner RP. Lyme disease: musculoskeletal manifestations. Rheum Dis Clin North Am

1989;15:649-56. 5. Berney S. Goldstein M, Bishko F. Clinical and diagnostic features of tuberculous arthritis. Am J Med

1972;53:36-42. 6. Cheatum DE, Hudman V, Jones SR. Chronic arthritis due to Mycobacterium infracellulare. Arthritis Rheum 1976; 19: 777-81. 7. Marchevsky AM, Damsker B, Green S, Tepper S. The clinicopathological spectrum of non-tuberculous mycobacterial osteoarticular infections. J Bone Joint Surg [Am] 1985; 67: 925-9. 8. Halleran WJ, Martin NL. Nontuberculous mycobacterial arthritis: report of a chronic case. J Kans Med Sot 1982; 83: 284-6. 9. Wallace R. Cohen AS. Tuberculous arthritis: a report of two cases with review of biopsy and synovial fluid findings. Am J Med 1976; 61: 277-82. 10. Hoffman GS, Myers RL. Stark FR, Thoen CO. Septic arthritis associated with Mycobacterium avium: a case report and literature review. J Rheumatol 1978; 5: 199-209. 11. Messner RP. Arthritis due to mycobacteria, fungi, and parasites. In: McCarty DJ. ed. Arthritis and allied conditions-textbook of rheumatology. 1 Ith ed. Philadelphia: Lea & Febiger, 1989: 1925-37. 12. Snydman DR, Schenkein DP. Berardi VP, Lastavita CC, Pariser KM. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Ann Intern Med 1986; 104: 798-800. Submitted

June 15.1990,

and accepted

August 28, 1990

The Reply:

I would like to respond to the questions raised by Dr. Akama concerning the patient reported with reactive arthritis following MA1 infection. Although no biopsy or synovial culture of the joint was undertaken to definitively exclude direct infection, the fact that the joint inflammation completely disappeared after 1 week and remained so without administration of anti-inflammatory agents and well before antituberculous therapy was begun argued clinically against a direct infection. Therefore, no biopsy was done. Dr. Akama questions whether the patient had another form of arthritis or underlying connective tissue disease because she had Raynaud’s phenomenon and of Medicine

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livedo reticularis. The patient has now been followed for 2 years with no evidence of other disease. His comment that most types of reactive arthritis are polyarticular may be true, but the dogmatic position he takes equating reactive arthritis with polyarthritis and infectious arthritis with monoarthritis is fallacious. There is no question that reactive arthritis including Reiter’s syndrome and Lyme disease may be monoarticular. Finally, with regard to his suggestion that this condition be called “nontuberculous mycobacterial rheumatism,” I fail to see how the term “rheumatism” is more clinically useful than “reactive arthritis.” J. MARICIC? M.D. University of Amona Tucson, Arizona

MICHAEL

USE OF /?-BLOCKERSIN THYROTOXICPATIENTS WITH HEART FAILURE To the Editor:

In their recent articles examining the relationship between the thyroid and the cardiovascular system, Levey and Klein (Am J Med 1990; 88: 642-6) as well as Ladenson (Am J Med 1990; 88: 638-41) propose that judicious use of /?blockers in thyrotoxic patients with heart failure may be beneficial, particularly in controlling rapid heart rate and tachyarrhythmias. However, the large potential risk associated with such use of P-blockers is illustrated by the findings of Ikram [1,2], who administered 2 mg of propranolol intravenously to seven thyrotoxic patients with heart failure and no underlying cause of heart disease other than the thyrotoxicosis itself. In these patients, administration of the pblocker caused the mean right atria1 pressure to increase from 11.9 to 20.6 mm Hg and the mean pulmonary artery diastolic pressure to rise from 13.6 to 28.2 mm