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Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin
7 Infectious Diseases Newsletter 10(1) January1991 peritonsillar abscess 3 years ago, which was drained by his general practitioner and from which we do not have any reference of microbiological studies. The oropharyngeal exploration showed a peritonsiUar abscess, that was drained, material obtained being sent for microbiological study. Treatment with tobramycin (100 mg/12 h) and clindamycin (600 mg/12 h) for 7 days was instituted, the patient being discharged from the hospital without complications.
Laboratory Results Samples obtained from the drainage were processed for detection of aerobic and anaerobic bacteria. After 24 h a massive growth of white-greyish, oxidase- and catalase-positive colonies in chocolate-agar and blood-agar were observed. No growth was observed on plates incubated under anaerobic conditions. The gram stain showed gram-negative diplococci, which grew well on nutrient agar at 35°C and showed mild growth on New York agar at 35°C and on blood agar, under aerobic conditions, at 22°C. The microorganism did not produce acid from glucose, maltose, lactose, sucrose, or fructose and did not reduce nitrate to nitrite, produce DNAse, or show polisaccharide synthesis, but did
reduce nitrate to nitrogen and did not produce beta-lactamase. So, the microorganism was identified as Neisseria cinerea.
Comment N. cinerea is usually considered as a
nonpathogenic microorganism, and a very small number of infections caused by N. cinerea have been published. The presence of the microorganism in the oropharynx seems to be frequent, being isolated from onethird to one-fourth of population. Nevertheless, no cases of oropharyngeal pathology have been described until now. Unless N. cinerea is repeatedly isolated from the oropharynx of homosexual men, this does not seem to be related to any kind of sexual activity, as genitourinary isolation is quite infrequent. One of the main lessons to be learned from this case is the care that must be taken not to identify N. cinerea as N. gonorrhoeae, mainly when the microorganism grows on selective media, such as New York agar, and from a location from which N. gonorrhoeae may be isolated (urethra, oropharynx, conjunctiva) but when history given by the patient does not justify the isolation of N. gonorrhoeae. In these cases, the limita-
tions of rapid identification systems must be taken in account, and an exceedingly accurate test must be performed.
Bibliography Bourbeau P, Holla V, Piemontese S: Ophtalmia neonatorum caused by Neisseria cinerea. J Clin Microbiol 28:1640-1641, 1990. Clausen CR, Knapp JS, Totten PA: Lymphadenitis due to Neisseria cinerea. Lancet i:908, 1984. Dossett JH, Appelbaum PC, Knapp JS, Totten PA: Proctitis associated with Neisseria cinerea misidentified as Neisseria gonorrhoeae in a child. J Clin Microbiol 21:575-577, 1985. Fisher MC: Conjuntivitis in children. Pediatr Clin North Am 34:1447-1455, 1987. Knapp JS, Hook HI EW: Prevalence and persistence of Neisseria cinerea and other Neisseria spp. in adults. J Clin Microbiol 26:896-900, 1988. Stefenson G, Pederson S: Neisseria cinerea infection in a neonate. Suspected gonococcal infection. Ugeskr Laeger 147:3810, 1985. JA Garcia-Rodriguez JE Garcfa Sanchez JL Mufioz Bellido E Garcfa Sanchez 1 Garc~a Garcia M' A Ramos Macias Hospital Clinico Universitario Salamanca, SPAIN
COMMENTS ON CURRENT PUBLICATIONS Chiu J, Nussbaum J, Bozzette S, et
al: Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin. Ann Intern Med 113:358361, 1990. This is a report of 17 patients with AIDS who had at least two consecutive blood cultures positive for M. avium complex, who had not been previously treated with antituberculous medications, and who were treated with combination therapy using ami-
kacin, etharnbutol, rifampin, and ciprofloxacin. During treatment, the geometric mean colony count from blood cultures decreased from 537 ml to 14 ml (p < 0.001) after 4 weeks of therapy. This microbiologic suppression was associated with a decrease in systemic symptoms related to M. avium complex infection. The authors conclude that mycobacterial load and systemic symptoms in AIDS patients infected with M. avium complex can be effectively reduced by a regimen containing amikacin, ethambutol, rifampin, and ciprofloxacin. © 1991 Elsevier Science Publishing Co., Inc. 0278-2316/91/$0.00 + 2.20
Comment The treatment of M. avium complex infection in AIDS patients has been disappointing. This study is importam for two reasons. First, the results clearly suggest that the morbidity associated with disseminated M. avium complex infection is related to mycobacterial load and can be reduced with appropriate regimens that suppress mycobacterial growth. Second, the combination of amikacin, ethambutol, rifampin, and ciprofloxacin was found to reduce bacteremia and symptoms. In this study, most patients responded
8 Infectious Diseases Newsletter 10(1) January 1991
within the first 4 weeks of therapy. After 4 weeks of therapy, the withdrawal of amikacin and the continuation of the other three oral agents was able to sustain the suppression of M. avium complex. Not all patients completely cleared their bacteremia although prolonged therapy might achieve this. The results of this study are encouraging and further investigation of this regimen is warranted. CWS []
Dorfman DH, Glaser JH: Congenital syphilis presenting in infants after the newborn period. N Engl J Med 323:1299-1302, 1990. This report describes seven infants seen during 1 year who were diagnosed as having congenital syphilis at 3-14 weeks of age, when symptoms developed. These infants' charts were reviewed in order to ascertain the reasons for the failure to diagnose syphilis at birth and to identify the signs and symptoms of congenital syphilis in this group of infants. At
Aims and Scope The Infectious Diseases Newsletter seeks to provide concise reports of the current state of knowledge and practice in infectious diseases. Diverse sources are tapped, the primary consideration being the relevance of the information that is gained. The intended audience includes physicians, nurses, and laboratory personnel who participate in the diagnosis, treatment, and prevention of infectious diseases. Such broad dissemination is warranted by the essential, yet interdependent, nature of the efforts of those health care providers whose concern is patients with infectious diseases.
delivery, four of the seven infants and their mothers had negative plasmareagin tests for syphilis. The other three mothers had been seronegative during the pregnancy and were therefore not tested at delivery; two of these infants were seronegative at birth and one was not tested. The infants were not symptomatic until 3 and 14 weeks of age; at this time all seven infants and five mothers available for testing were found to be seropositive for syphilis. Four infants presented with a diffuse maculopapular rash that involved the palms and soles. The other three infants presented with fever and were found to have aseptic meningitis although none had symptoms referable to central nervous system (CNS) infection. All infants were noted to have hepatomegaly and abnormal liver function tests. All infants had anemia, leukocytosis, and monocytosis. Rhinitis was noted in four infants; darkfield microscopic examination was not done. Radiologic evidence of bone involvement was seen in one-half of six infants who underwent radiologic studies, but no child had symptoms of bone involvement. Finally, a JarishHerxheimer reaction consisting only of a marked, sudden elevation of
temperature was seen in all infants within 2-6 h of receiving the first dose of antibiotics. Comment There has been a marked increase in the incidence of syphilis in the United States in the past few years. An especially large increase in the frequency of syphilis among young women has been responsible for a concomitant increase in the incidence of congenital syphilis. This report shows that acquisition of syphilis toward the end of pregnancy may result in late-presenting (3-14 weeks) in infants who, along with their mothers, may be seronegative at the time of delivery. Clearly, it is advisable to test all mothers during pregnancy (first prenatal visit and during the third trimester in high-risk situations) and to test all mothers and babies at delivery. Some cases of congenital syphilis will still go undiagnosed until symptoms develop in the infant. Accordingly, infants who present with a characteristic rash and/or who present with aseptic meningitis, hepatomegaly, or hematologic abnormalities should be retested for syphilis, even if previous serology has been negative. CWS
General Information Infectious Diseases Newsletter is published monthly by Elsevier Science Publishing Co., Inc., 655 Avenue of the Americas, New York, New York 10010. Please see inside front cover for subscription information. This newsletter has been registered with the Copyright Clearance Center Inc. Consent is given for copying of articles for personal or internal use, or for the personal or internal use of specific clients. This consent is given on the condition that the copier pay through the Center the per-page fee stated in the code on each page for copying beyond that permitted by the US Copyright Law. If no code appears on an article, the author has not given broad consent to copy and permission to copy must be obtained directly from the author. This consent does not extend to other kinds of copying, such as for general distribution, resale, advertising and promotional purposes, or for creating new collective works. Address orders, changes of address, and claims for missing issues to Journals Fulfillment Department, Elsevier Science Publishing Co., Inc., 655 Avenue of the Americas, New York, New York 10010. Claims for missing issues can be honored only up to three months for domestic addresses and six months for foreign addresses. Duplicate copies will not be sent to replace those undelivered because of failure to notify Elsevier of change of address. Address editorial correspondence to Charles W. Stratton, MD, Director of Clinical Microbiology, Department of Pathology, Vanderbilt University Medical Center, C3321 Medical Center North, Nashville, TN 37232.
Infectious Diseases Newsletter is included in BIOSIS. © 1991 Elsevier Science Publishing Co., Inc. 0278-2316/91/$0.00 + 2.20
Laboratory Results Samples obtained from the drainage were processed for detection of aerobic and anaerobic bacteria. After 24 h a massive growth of white-greyish, oxidase- and catalase-positive colonies in chocolate-agar and blood-agar were observed. No growth was observed on plates incubated under anaerobic conditions. The gram stain showed gram-negative diplococci, which grew well on nutrient agar at 35°C and showed mild growth on New York agar at 35°C and on blood agar, under aerobic conditions, at 22°C. The microorganism did not produce acid from glucose, maltose, lactose, sucrose, or fructose and did not reduce nitrate to nitrite, produce DNAse, or show polisaccharide synthesis, but did
reduce nitrate to nitrogen and did not produce beta-lactamase. So, the microorganism was identified as Neisseria cinerea.
Comment N. cinerea is usually considered as a
nonpathogenic microorganism, and a very small number of infections caused by N. cinerea have been published. The presence of the microorganism in the oropharynx seems to be frequent, being isolated from onethird to one-fourth of population. Nevertheless, no cases of oropharyngeal pathology have been described until now. Unless N. cinerea is repeatedly isolated from the oropharynx of homosexual men, this does not seem to be related to any kind of sexual activity, as genitourinary isolation is quite infrequent. One of the main lessons to be learned from this case is the care that must be taken not to identify N. cinerea as N. gonorrhoeae, mainly when the microorganism grows on selective media, such as New York agar, and from a location from which N. gonorrhoeae may be isolated (urethra, oropharynx, conjunctiva) but when history given by the patient does not justify the isolation of N. gonorrhoeae. In these cases, the limita-
tions of rapid identification systems must be taken in account, and an exceedingly accurate test must be performed.
Bibliography Bourbeau P, Holla V, Piemontese S: Ophtalmia neonatorum caused by Neisseria cinerea. J Clin Microbiol 28:1640-1641, 1990. Clausen CR, Knapp JS, Totten PA: Lymphadenitis due to Neisseria cinerea. Lancet i:908, 1984. Dossett JH, Appelbaum PC, Knapp JS, Totten PA: Proctitis associated with Neisseria cinerea misidentified as Neisseria gonorrhoeae in a child. J Clin Microbiol 21:575-577, 1985. Fisher MC: Conjuntivitis in children. Pediatr Clin North Am 34:1447-1455, 1987. Knapp JS, Hook HI EW: Prevalence and persistence of Neisseria cinerea and other Neisseria spp. in adults. J Clin Microbiol 26:896-900, 1988. Stefenson G, Pederson S: Neisseria cinerea infection in a neonate. Suspected gonococcal infection. Ugeskr Laeger 147:3810, 1985. JA Garcia-Rodriguez JE Garcfa Sanchez JL Mufioz Bellido E Garcfa Sanchez 1 Garc~a Garcia M' A Ramos Macias Hospital Clinico Universitario Salamanca, SPAIN
COMMENTS ON CURRENT PUBLICATIONS Chiu J, Nussbaum J, Bozzette S, et
al: Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin. Ann Intern Med 113:358361, 1990. This is a report of 17 patients with AIDS who had at least two consecutive blood cultures positive for M. avium complex, who had not been previously treated with antituberculous medications, and who were treated with combination therapy using ami-
kacin, etharnbutol, rifampin, and ciprofloxacin. During treatment, the geometric mean colony count from blood cultures decreased from 537 ml to 14 ml (p < 0.001) after 4 weeks of therapy. This microbiologic suppression was associated with a decrease in systemic symptoms related to M. avium complex infection. The authors conclude that mycobacterial load and systemic symptoms in AIDS patients infected with M. avium complex can be effectively reduced by a regimen containing amikacin, ethambutol, rifampin, and ciprofloxacin. © 1991 Elsevier Science Publishing Co., Inc. 0278-2316/91/$0.00 + 2.20
Comment The treatment of M. avium complex infection in AIDS patients has been disappointing. This study is importam for two reasons. First, the results clearly suggest that the morbidity associated with disseminated M. avium complex infection is related to mycobacterial load and can be reduced with appropriate regimens that suppress mycobacterial growth. Second, the combination of amikacin, ethambutol, rifampin, and ciprofloxacin was found to reduce bacteremia and symptoms. In this study, most patients responded
8 Infectious Diseases Newsletter 10(1) January 1991
within the first 4 weeks of therapy. After 4 weeks of therapy, the withdrawal of amikacin and the continuation of the other three oral agents was able to sustain the suppression of M. avium complex. Not all patients completely cleared their bacteremia although prolonged therapy might achieve this. The results of this study are encouraging and further investigation of this regimen is warranted. CWS []
Dorfman DH, Glaser JH: Congenital syphilis presenting in infants after the newborn period. N Engl J Med 323:1299-1302, 1990. This report describes seven infants seen during 1 year who were diagnosed as having congenital syphilis at 3-14 weeks of age, when symptoms developed. These infants' charts were reviewed in order to ascertain the reasons for the failure to diagnose syphilis at birth and to identify the signs and symptoms of congenital syphilis in this group of infants. At
Aims and Scope The Infectious Diseases Newsletter seeks to provide concise reports of the current state of knowledge and practice in infectious diseases. Diverse sources are tapped, the primary consideration being the relevance of the information that is gained. The intended audience includes physicians, nurses, and laboratory personnel who participate in the diagnosis, treatment, and prevention of infectious diseases. Such broad dissemination is warranted by the essential, yet interdependent, nature of the efforts of those health care providers whose concern is patients with infectious diseases.
delivery, four of the seven infants and their mothers had negative plasmareagin tests for syphilis. The other three mothers had been seronegative during the pregnancy and were therefore not tested at delivery; two of these infants were seronegative at birth and one was not tested. The infants were not symptomatic until 3 and 14 weeks of age; at this time all seven infants and five mothers available for testing were found to be seropositive for syphilis. Four infants presented with a diffuse maculopapular rash that involved the palms and soles. The other three infants presented with fever and were found to have aseptic meningitis although none had symptoms referable to central nervous system (CNS) infection. All infants were noted to have hepatomegaly and abnormal liver function tests. All infants had anemia, leukocytosis, and monocytosis. Rhinitis was noted in four infants; darkfield microscopic examination was not done. Radiologic evidence of bone involvement was seen in one-half of six infants who underwent radiologic studies, but no child had symptoms of bone involvement. Finally, a JarishHerxheimer reaction consisting only of a marked, sudden elevation of
temperature was seen in all infants within 2-6 h of receiving the first dose of antibiotics. Comment There has been a marked increase in the incidence of syphilis in the United States in the past few years. An especially large increase in the frequency of syphilis among young women has been responsible for a concomitant increase in the incidence of congenital syphilis. This report shows that acquisition of syphilis toward the end of pregnancy may result in late-presenting (3-14 weeks) in infants who, along with their mothers, may be seronegative at the time of delivery. Clearly, it is advisable to test all mothers during pregnancy (first prenatal visit and during the third trimester in high-risk situations) and to test all mothers and babies at delivery. Some cases of congenital syphilis will still go undiagnosed until symptoms develop in the infant. Accordingly, infants who present with a characteristic rash and/or who present with aseptic meningitis, hepatomegaly, or hematologic abnormalities should be retested for syphilis, even if previous serology has been negative. CWS
General Information Infectious Diseases Newsletter is published monthly by Elsevier Science Publishing Co., Inc., 655 Avenue of the Americas, New York, New York 10010. Please see inside front cover for subscription information. This newsletter has been registered with the Copyright Clearance Center Inc. Consent is given for copying of articles for personal or internal use, or for the personal or internal use of specific clients. This consent is given on the condition that the copier pay through the Center the per-page fee stated in the code on each page for copying beyond that permitted by the US Copyright Law. If no code appears on an article, the author has not given broad consent to copy and permission to copy must be obtained directly from the author. This consent does not extend to other kinds of copying, such as for general distribution, resale, advertising and promotional purposes, or for creating new collective works. Address orders, changes of address, and claims for missing issues to Journals Fulfillment Department, Elsevier Science Publishing Co., Inc., 655 Avenue of the Americas, New York, New York 10010. Claims for missing issues can be honored only up to three months for domestic addresses and six months for foreign addresses. Duplicate copies will not be sent to replace those undelivered because of failure to notify Elsevier of change of address. Address editorial correspondence to Charles W. Stratton, MD, Director of Clinical Microbiology, Department of Pathology, Vanderbilt University Medical Center, C3321 Medical Center North, Nashville, TN 37232.
Infectious Diseases Newsletter is included in BIOSIS. © 1991 Elsevier Science Publishing Co., Inc. 0278-2316/91/$0.00 + 2.20