Dial Hewlett

Central nervous system involvement in patients with acquired immune deficiency syndrome (AIDS)

ABSTRACT – Central nervous system involvement occurred in 28 of 121 patients with acquired immune deficiency syndrome (AIDS). The major risk factor in this AIDS population was intravenous drug abuse (64%). A neurologic symptom or disability was the principal reason for hospitalization in 16 cases (57%). Three patients had primary lymphoma of the brain and the remainder had opportunistic infections. Patients with focal neurological features usually had toxoplasmosis. Progressive headache and meningeal signs occurred with cryptococcosis. A progressive subacute dementia was probably due to cytomegalovirus. Other infections included atypical mycobacteria, candida, herpes zoster and possible progressive multifocal leukoencephalopathy.

Limited tolerance of ofloxacin and pyrazinamide prophylaxis against tuberculosis.

To the Editor: An outbreak of tuberculosis resistant to rifampin, isoniazid, streptomycin, and ethambutol occurred in our institution1 in association with conversions among our health care workers ...

Mycobacterium tuberculosis infection in the acquired immunodeficiency syndrome. A review of 14 patients.

The clinical findings in 13 drug abusers and one homosexual man with tuberculosis and the acquired immunodeficiency syndrome (AIDS) from New York City are described. Tuberculosis preceded the diagnosis of AIDS in nine of the 14 patients by a mean of 7 months and occurred within the same month in the remaining five. The presence of thrush, generalised lymphadenopathy, lymphopenia, cutaneous anergy and chest radiographs showing hilar adenopathy and/or lower lobe infiltrates was common among the patients in whom tuberculosis preceded AIDS. Eight of our patients had extra-pulmonary tuberculosis, six had disseminated tuberculosis and five had tuberculous lymphadenitis. Cultures of tissue biopsies may be positive for Mycobacterium tuberculosis despite the absence of acid fast bacilli or granulomas on microscopic examination. Tuberculosis generally responded to chemotherapy, but the majority of patients died from opportunist infections.

Superinfection with Rifampin-Isoniazid-Streptomycin-Ethambutol (RISE)-resistant Tuberculosis in Three Patients with AIDS: Confirmation by Polymerase Chain Reaction Fingerprinting

Reinfection with new strains of Mycobacterium tuberculosis has been reported [1-4]. Exogenous reinfection with M. tuberculosis resistant to isoniazid and streptomycin played an important role in an outbreak occurring in a homeless shelter [5]. Recently, restriction fragment-length polymorphism analysis has been used to show exogenous M. tuberculosis reinfection of patients with the acquired immunodeficiency syndrome (AIDS) who have multidrug-resistant tuberculosis that occurred during therapy for the initial drug-sensitive infection [6, 7]. We describe three additional patients in whom rifampin-isoniazid-streptomycin-ethambutol (RISE)-resistant tuberculosis occurred during therapy for drug-susceptible tuberculosis. This was documented by DNA fingerprinting using the mixed-linker polymerase chain reaction (PCR) technique. Methods Mycobacterium tuberculosis was isolated on Lowenstein-Jensen slants and identified by the AccuProbe System (Gen-Probe, Inc., San Diego, California). Susceptibility testing was done by the New York City Department of Health Bureau of Laboratories. For DNA fingerprinting, mycobacterial growth was washed from the Lowenstein-Jensen slants, and the cells were lysed by beating with siliconized zirconium beads and chloroform in a Mickle apparatus (H. Mickle, Gromshall, Surrey, United Kingdom). Mixed-linker PCR was done as previously described [8] at the Centers for Disease Control and Prevention. Results A review of microbiology laboratory data from December 1990 to November 1992 showed 250 patients with tuberculosis identified by our institution. Three patients with RISE-resistant tuberculosis had paired isolates with markedly discordant susceptibility profiles, and DNA fingerprinting of the original isolates by mixed-linker PCR showed unique patterns that differed from the common pattern of the nosocomial superinfecting RISE-resistant M. tuberculosis isolates (Figure 1). The three patients are described below. Figure 1. Mixed-linker fingerprints of Mycobacterium tuberculosis isolates. Case 1 A 32-year-old man with human immunodeficiency virus (HIV) infection presented in August 1991 with Staphylococcus aureus endocarditis. He received 4 weeks of therapy in an AIDS inpatient ward, which was the epicenter of an outbreak of RISE-resistant tuberculosis [9]. The patient was discharged but then recalled when a culture of bronchoalveolar lavage fluid showed M. tuberculosis. He received isoniazid, rifampin, and pyrazinamide for drug-susceptible tuberculosis. In July 1993, the patient was readmitted because of weight loss, fever, and cough. The CD4 lymphocyte count was 91 cells/L. A sputum culture subsequently grew M. tuberculosis resistant to RISE, pyrazinamide, kanamycin, and ethionamide. Case 2 A 28-year-old woman with HIV infection was prescribed isoniazid in June 1991 because of a positive tuberculin skin-test result. Two months later, she was hospitalized with fever, headache, and cough. The CD4 count was 172 cells/L. Examination of cerebrospinal fluid showed lymphocytic meningitis, and first-line antituberculous agents were administered. She was readmitted in December 1991 because of a generalized tonic-clonic seizure. Sputum and cerebrospinal fluid cultures grew M. tuberculosis that was resistant to isoniazid and susceptible to rifampin, pyrazinamide, ethambutol, and streptomycin. The patient improved and was discharged in March 1992. During her hospitalizations, she was exposed to RISE-resistant tuberculosis. In December 1992, the patient was readmitted; she died 4 weeks later. Mycobacterium tuberculosis subsequently grew in culture and was resistant to RISE and pyrazinamide. Case 3 A 28-year-old man with HIV infection had a positive tuberculin skin-test result in 1987. He presented in November 1991 with fever, productive cough, and a CD4 lymphocyte count of 3 cells/L. Bronchoscopy showed Pneumocystis carinii. Sputum cultures grew drug-susceptible M. tuberculosis. Isoniazid, rifampin, pyrazinamide, and ethambutol were administered. The patient was readmitted in March 1992. During his clinic visits and hospitalizations, the patient was exposed to many patients with RISE-resistant tuberculosis. Mycobacterium avium complex was identified in the sputum, and ciprofloxacin and amikacin were added to his drug regimen. He died 4 months later. A sputum culture subsequently grew M. tuberculosis that was resistant to RISE, ethionamide, and kanamycin and was susceptible to capreomycin, cycloserine, and ciprofloxacin. Discussion Superinfection with RISE-resistant tuberculosis occurred in these three patients with AIDS despite therapy for concurrent drug-susceptible tuberculosis. Because the initial isolates of M. tuberculosis were no longer viable on subculture, standard DNA fingerprinting was not possible. The use of a new technique, DNA fingerprint analysis by mixed-linker PCR, facilitated the rapid recognition of the outbreak strain and enabled us to unambiguously differentiate the original isolates. Mixed-linker PCR is a modified single-site PCR technique that specifically amplifies HhaI restriction fragments containing one end of IS6110 and the adjacent flanking segment. The resulting fingerprint pattern is compatible with that obtained by the standard restriction fragment-length polymorphism technique, consisting of restriction with PvuII, Southern blotting, and hybridization with an IS6110-specific probe [10]. The waning protective immunity associated with AIDS may facilitate superinfection or exogenous reinfection in patients previously effectively treated or receiving therapy for tuberculosis. Our findings strongly argue against placing more than one patient with tuberculosis in one room. Population-based studies are required to quantify the incidence of exogenous reinfection or superinfection to determine if it poses a substantial public health threat. Mixed-linker PCR should prove to be a powerful tool in doing the necessary epidemiologic studies.

Lack of Effect of Oral Acyclovir on Prevention of Aphthous Stomatitis

Aphthous stomatitis (canker sores) is a common cause of recurrent mouth ulceration. The effect of long-term oral acyclovir therapy on aphthous stomatitis recurrences was evaluated in 44 patients who were in a double-blind treatment trial for recurrent genital Herpes simplex infections. Twenty-five subjects received oral acyclovir daily for one year, while 19 received the drug only during outbreaks of herpes. The number of patients who experienced recurrences of aphthous stomatitis and the frequency and duration of attacks per patient were not significantly different between groups. Furthermore, no consistent change in attack rate was observed in members of either group compared to that reported before they had entered the trial. We conclude that oral acyclovir is not effective for prevention of recurrent aphthous stomatitis in most patients.

CLINICAL EXPERIENCE WITH RIFAMPIN-ISONIAZID-STREPTOMYCIN-ETHAMBUTOL (RISE)-RESISTANT TUBERCULOSIS

We review demographic and clinical features of 55 patients with rifampin-isoniazid-streptomycin-ethambutol (RISE)-resistant tuberculosis in our hospital from April 1, 1991, to July 31, 1993. Fifty-one of the 55 patients (median age, 36 years) were seropositive for human immunodeficiency virus (HIV), and 49 had AIDS. Among the HIV-infected patients, the median CD4 cell count was 31/mm3. Forty-two patients died during the study period. Exogenous reinfection or superinfection with RISE-resistant tuberculosis occurred in 12 of 55 patients with a prior history of tuberculosis infection or disease. Fourteen of 55 received appropriate therapy, eight of whom became culture negative after a median of 68 days. Twelve of the 14 appropriately treated patients survived at least 6 months. When appropriately managed, even severely immunosuppressed individuals with HIV infection may have their RISE-resistant tuberculosis successfully controlled or eradicated. This infection however, remains highly lethal in the majority of patients with AIDS. Patients remain infectious for prolonged periods, even after appropriate therapy has been initiated.