lID 1991;164 (August)
Correspondence
Randomized Trial of 5-Day Rifampin versus I-Day Doxycycline Therapy for Mediterranean Spotted Fever CoHeague~-Mediterranean spotted fever (MSF) is a tickborne rickettsiosis caused by Rickettsia conorii. In previous studies [ 1, 2] we demonstrated the efficacy of two single doses of doxycycline for MSF. This therapeutic regimen offersadditional advantages given the greater convenience, decreased cost, and minimal risk of staining ofteeth in children. Thus, l-day doxycycline therapy is the current treatment of choice at our institution for both adults and children with MSF. To date 134 consecutive patients have received this schedule, all with good results. Because tetracyclines may cause untoward effects in pregnant women and allergic pctients, alternative treatments have been
Patients or their parents gave informed consent; the protocol was approved by the Institutional Ethical Committee. Reprints and correspondence: Dr. F. Bella, Department ofInternal Medicine. Hospital de Terrassa, Ctra. de Torrebonica sin, 08227 Terrassa, Barcelona. Spain. The Journal of Infectious Diseases 1991;164:433-4 © 1991 by The University of Chicago. All rights reserved. 0022-1899/91/6402-0039$01.00
symptoms, hepatosplenomegaly, and a similar mycobacterium seen by electron microscopy of autopsied tissue. All attempts to culture the putative mycobacterium on solid media failed, yet thin-layer chromatography revealed the presence of a-, a'· and keto-mycolates similar to that of M. simiae [5]. The clinical pictures of that patient and ours are similar to those of patients with disseminated MAC with intraabdominal adenopathy, cholestasis, and progressive anemia and wasting. In a given patient, the coexistence of various mycobacterial species makes identification of mycobacterial isolates imperative to guide appropriate therapy.
Ramon A. Torres, Jill Nord, Richard Feldman, Vincent LaBombardi, and Michael Barr St. Vincent's Hospital and Medical Center of New York. New York City
References l. Bell RC, Higuchi JH, Donovan WN, Krasnow I, Johanson WG. Mycobacterium simiae: clinical features and follow-up of twenty-four patients. Am Rev Respir Dis 1983;127:35-8. 2. Rose HD, DorffGJ, Lauwasser M, Sheth NK. Pulmonary and disseminated Mycobacterium simiae infection in humans. Am Rev Respir Dis 1982;126:1110-3. 3. Levy-Frebault Y, Pangan B, Bure A, Katlama C, Marche C, David HL. Mycobacterium simiae and Mycobacterium avium-M. intracellulare mixed infection in acquired immune deficiency syndrome. J Clin Microbiol 1987;25: 154-7. 4. Wolinsky E. Nontuberculous mycobacteria and associated disease. Am Rev Respir Dis 1979; II 9: 107. 5. Hirschel B, Chang HR, Mach N. Fatal infection with a novel, unidentified mycobacterium in a man with the acquired immunodeficiency syndrome. N Engl J Med 1990;323: l09-13.
evaluated. The in vitro activity of chloramphenicol is similar to that of tetracyclines, but the risk of bone marrow toxicity may argue against its use in such a generally benign disease. The potential usefulness of new quinolone compounds was recently reported [3], although these drugs should not be prescribed for pregnant women or children. Josamycin is a useful therapeutic alternative that may be particularly convenient for pregnant women and patients with an allergic history to tetracyclines [2]. In the past few years a high susceptibility of R. conorii to rifampin has been reported, with an MIC of 0.25 J,Lg/ml [4], but comparative clinical trials using rifampin have not been reported. To evaluate the clinical usefulness of rifampin, we prospectively studied 32 consecutive patients with MSF, confirmed by indirect immunofluorescence, who were hospitalized during the summer of 1989. Pregnant patients and those who received antibiotics in the week preceding the study or had a history of allergy to tetracyclines or rifampin were excluded. The study was designed to include 52 patients to avoid a type II error, but at the end of the first year, differences between groups were significant and the trial was stopped. Patients were randomized at admission into two groups, according to a set of computer-generated random numbers. Pa-
Downloaded from http://jid.oxfordjournals.org/ at University of Illinois at Urbana-Champaign on September 6, 2015
therapy, with progressive wasting and debilitation. Identification of bacilli isolated from blood cultures and liver biopsy tissue during the period of therapy with ethionamide and cycloserine revealed MAC by Gen-Probe nucleic acid hybridization assay (GenProbe, San Diego, CA). The test results for these isolates yielded hybridization percentages of 48.5%-49.5% for M. avium and 1.1%-1.8% for Mycobacterium intracellulare. The colonial morphology of the isolates was typical of MAC. In the experience of one of us, cross-reactions with other species of mycobacteria (other than Mycobacterium paratuberculosis) at hybridization levels of 50% have not been encountered. Conversely, hybridization rates of < 1% with Gen-Probe were seen with the M. simiae isolates from the same patient. The patient died of bacterial sepsis and progressive HIV encephalopathy. Permission for an autopsy was denied. M. simiae was originally recovered from rhesus monkeys imported from India [1]. It has subsequently been isolated from sputum cultures of hospitalized patients, tap water, and bronchial washings from a patient with previous contact with monkeys [2-4]. In most series, M. simiaewas not pathogenic and was recovered casually from sputum or bronchial washings of patients with underlying pulmonary disease, such as bronchogenic carcinoma and chronic obstructive lung disease. HIV-induced immunodeficiency, compounded by use of corticosteroids, may have led to recrudescence of infection with hematogenous dissemination and subsequent lymphatic and pulmonary involvement. M. simiae is resistant to all standard anti mycobacterial drugs except ethionamide and cycloserine. Our patient cleared the M. simiae from the blood after therapy but deteriorated clinically, probably from disseminated MAC infection. Recently, a patient in Switzerland displayed fulminant gastrointestinal
433
434
Correspondence
JID 1991;164 (August)
at present, the known sensitivity of R. conorii to rifampin is based on a small number of isolates [4]. Thus, the presence of some R. conorii strains resistant to rifampin might be postulated to explain our four therapeutic failures. However, in patients treated with rifampin, there was a delay in achieving apyrexia, suggesting a slower in vivo antirickettsial activity of rifampin rather than the existence of some resistant strains. The results of this study show that l-day doxycycline therapy is more effective than rifampin in treating MSF and that although rifampin may be an acceptable therapeutic alternative for some patients, there is a significant risk of delayed apyrexia when this drug is used.
Transient Acquired Factor II Deficiency with Mycoplasma pneumoniae Infection
A 72-year-old man who never bled abnormally in previous surgical procedures was admitted with fever, chills, cough, and myalgia of 4 days duration. On physical examination, he appeared ill and had a temperature of 39°C and bilateral pulmonary rales were heard. Laboratory findings included: hematocrit, 42%; white cell count, 14.8 X 109/1 with a shift to the left; and platelet count of 190 X 109/1. Coagulation tests revealed prothrombin activity that was 13% of normal and partial thromboplastin time of 103 s (control 29). Factor II assay showed
Correspondence
Randomized Trial of 5-Day Rifampin versus I-Day Doxycycline Therapy for Mediterranean Spotted Fever CoHeague~-Mediterranean spotted fever (MSF) is a tickborne rickettsiosis caused by Rickettsia conorii. In previous studies [ 1, 2] we demonstrated the efficacy of two single doses of doxycycline for MSF. This therapeutic regimen offersadditional advantages given the greater convenience, decreased cost, and minimal risk of staining ofteeth in children. Thus, l-day doxycycline therapy is the current treatment of choice at our institution for both adults and children with MSF. To date 134 consecutive patients have received this schedule, all with good results. Because tetracyclines may cause untoward effects in pregnant women and allergic pctients, alternative treatments have been
Patients or their parents gave informed consent; the protocol was approved by the Institutional Ethical Committee. Reprints and correspondence: Dr. F. Bella, Department ofInternal Medicine. Hospital de Terrassa, Ctra. de Torrebonica sin, 08227 Terrassa, Barcelona. Spain. The Journal of Infectious Diseases 1991;164:433-4 © 1991 by The University of Chicago. All rights reserved. 0022-1899/91/6402-0039$01.00
symptoms, hepatosplenomegaly, and a similar mycobacterium seen by electron microscopy of autopsied tissue. All attempts to culture the putative mycobacterium on solid media failed, yet thin-layer chromatography revealed the presence of a-, a'· and keto-mycolates similar to that of M. simiae [5]. The clinical pictures of that patient and ours are similar to those of patients with disseminated MAC with intraabdominal adenopathy, cholestasis, and progressive anemia and wasting. In a given patient, the coexistence of various mycobacterial species makes identification of mycobacterial isolates imperative to guide appropriate therapy.
Ramon A. Torres, Jill Nord, Richard Feldman, Vincent LaBombardi, and Michael Barr St. Vincent's Hospital and Medical Center of New York. New York City
References l. Bell RC, Higuchi JH, Donovan WN, Krasnow I, Johanson WG. Mycobacterium simiae: clinical features and follow-up of twenty-four patients. Am Rev Respir Dis 1983;127:35-8. 2. Rose HD, DorffGJ, Lauwasser M, Sheth NK. Pulmonary and disseminated Mycobacterium simiae infection in humans. Am Rev Respir Dis 1982;126:1110-3. 3. Levy-Frebault Y, Pangan B, Bure A, Katlama C, Marche C, David HL. Mycobacterium simiae and Mycobacterium avium-M. intracellulare mixed infection in acquired immune deficiency syndrome. J Clin Microbiol 1987;25: 154-7. 4. Wolinsky E. Nontuberculous mycobacteria and associated disease. Am Rev Respir Dis 1979; II 9: 107. 5. Hirschel B, Chang HR, Mach N. Fatal infection with a novel, unidentified mycobacterium in a man with the acquired immunodeficiency syndrome. N Engl J Med 1990;323: l09-13.
evaluated. The in vitro activity of chloramphenicol is similar to that of tetracyclines, but the risk of bone marrow toxicity may argue against its use in such a generally benign disease. The potential usefulness of new quinolone compounds was recently reported [3], although these drugs should not be prescribed for pregnant women or children. Josamycin is a useful therapeutic alternative that may be particularly convenient for pregnant women and patients with an allergic history to tetracyclines [2]. In the past few years a high susceptibility of R. conorii to rifampin has been reported, with an MIC of 0.25 J,Lg/ml [4], but comparative clinical trials using rifampin have not been reported. To evaluate the clinical usefulness of rifampin, we prospectively studied 32 consecutive patients with MSF, confirmed by indirect immunofluorescence, who were hospitalized during the summer of 1989. Pregnant patients and those who received antibiotics in the week preceding the study or had a history of allergy to tetracyclines or rifampin were excluded. The study was designed to include 52 patients to avoid a type II error, but at the end of the first year, differences between groups were significant and the trial was stopped. Patients were randomized at admission into two groups, according to a set of computer-generated random numbers. Pa-
Downloaded from http://jid.oxfordjournals.org/ at University of Illinois at Urbana-Champaign on September 6, 2015
therapy, with progressive wasting and debilitation. Identification of bacilli isolated from blood cultures and liver biopsy tissue during the period of therapy with ethionamide and cycloserine revealed MAC by Gen-Probe nucleic acid hybridization assay (GenProbe, San Diego, CA). The test results for these isolates yielded hybridization percentages of 48.5%-49.5% for M. avium and 1.1%-1.8% for Mycobacterium intracellulare. The colonial morphology of the isolates was typical of MAC. In the experience of one of us, cross-reactions with other species of mycobacteria (other than Mycobacterium paratuberculosis) at hybridization levels of 50% have not been encountered. Conversely, hybridization rates of < 1% with Gen-Probe were seen with the M. simiae isolates from the same patient. The patient died of bacterial sepsis and progressive HIV encephalopathy. Permission for an autopsy was denied. M. simiae was originally recovered from rhesus monkeys imported from India [1]. It has subsequently been isolated from sputum cultures of hospitalized patients, tap water, and bronchial washings from a patient with previous contact with monkeys [2-4]. In most series, M. simiaewas not pathogenic and was recovered casually from sputum or bronchial washings of patients with underlying pulmonary disease, such as bronchogenic carcinoma and chronic obstructive lung disease. HIV-induced immunodeficiency, compounded by use of corticosteroids, may have led to recrudescence of infection with hematogenous dissemination and subsequent lymphatic and pulmonary involvement. M. simiae is resistant to all standard anti mycobacterial drugs except ethionamide and cycloserine. Our patient cleared the M. simiae from the blood after therapy but deteriorated clinically, probably from disseminated MAC infection. Recently, a patient in Switzerland displayed fulminant gastrointestinal
433
434
Correspondence
JID 1991;164 (August)
at present, the known sensitivity of R. conorii to rifampin is based on a small number of isolates [4]. Thus, the presence of some R. conorii strains resistant to rifampin might be postulated to explain our four therapeutic failures. However, in patients treated with rifampin, there was a delay in achieving apyrexia, suggesting a slower in vivo antirickettsial activity of rifampin rather than the existence of some resistant strains. The results of this study show that l-day doxycycline therapy is more effective than rifampin in treating MSF and that although rifampin may be an acceptable therapeutic alternative for some patients, there is a significant risk of delayed apyrexia when this drug is used.
Transient Acquired Factor II Deficiency with Mycoplasma pneumoniae Infection
A 72-year-old man who never bled abnormally in previous surgical procedures was admitted with fever, chills, cough, and myalgia of 4 days duration. On physical examination, he appeared ill and had a temperature of 39°C and bilateral pulmonary rales were heard. Laboratory findings included: hematocrit, 42%; white cell count, 14.8 X 109/1 with a shift to the left; and platelet count of 190 X 109/1. Coagulation tests revealed prothrombin activity that was 13% of normal and partial thromboplastin time of 103 s (control 29). Factor II assay showed
