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Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, Zürich, Switzerland
Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland
Zürcher Hhenklinik Wald, Faltigberg, Switzerland
Institute of Diagnostic Radiology, University Hospital of Zürich, Zürich, Switzerland
ABSTRACT
We report the first case of a pulmonary infection with Mycobacterium sherrisii in a patient with advanced human immunodeficiency virus infection. Mycobacterium sherrisii is a newly described nontuberculous mycobacterium related to Mycobacterium simiae. Sequencing of the 16S rRNA gene was used for species identification. Treatment and antibiotic susceptibilities are described.
CASE REPORT
A 47-year-old African male was referred to our hospital after he tested positive for human immunodeficiency virus (HIV) infection. In the 2 years prior to diagnosis of HIV, he had noticed a progressive weight loss of 13 kg and a progressive generalized weakness. Virologic and immunologic studies revealed a CD4 cell count of 19 cells/μl (6% of total lymphocytes) and an HIV RNA level of 595,000 copies/ml. A laboratory workup showed an anemia (hemoglobin, 10.6 g/dl; normal range, 13.5 to 17.2) and a leukopenia with lymphocytopenia, while the remaining values (creatinine, lactic dehydrogenase, electrolytes, transaminases, bilirubin, and C-reactive protein) were all within normal range. The patient was afebrile, and physical examination was normal except for cachexia. A chest X ray was normal. A tuberculin test showed a negative result. Antiretroviral therapy with zidovudine, lamivudine, and ritonavir-boosted lopinavir was started. Within 3 weeks following the start of antiretroviral therapy, the patient complained about increasing abdominal pain and developed a productive cough, night sweats, diarrhea, and intermittent fevers. His anemia worsened. The C-reactive protein increased to 75 mg/liter, and the blood sedimentation rate to 130 mm/h. Zidovudine was replaced by stavudine. An initial sputum sample was negative for Pneumocystis carinii and acid-fast microorganisms by direct microscopy. A chest computed-tomography scan revealed ground-glass-like interstitial infiltrate in the right upper lobe and markedly enlarged lymph nodes in the right hilus and along both bronchi (Fig. 1). The patient was hospitalized in a regional hospital for further diagnosis, treatment, and isolation. Therapy for presumptive tuberculosis was initiated with rifampin, ethambutol, isoniazid, and pyrazinamide. A blood culture was negative. While a second sputum taken 1 day later again did not show acid-fast bacilli by microscopy, a third sputum taken 1 week after symptoms began now demonstrated acid-fast bacilli by microscopy.
A Mycobacteria Growth Indicator Tube (Becton Dickinson Microbiology Systems, Sparks, MD) culture of the second sputum turned positive for acid-fast bacilli after 8 days of incubation. Part of the Mycobacteria Growth Indicator Tube culture was inactivated by incubation at 90°C for 30 min. DNA was extracted using the InstaGene matrix according to the instructions of the manufacturer (Bio-Rad, Glattbrugg, Switzerland). A 1,000-bp fragment of the 16S rRNA gene was amplified using primers 264 (5' TGC ACA CAG GCC ACA AGG GA) and 283 (5' GAG TTT GAT CCT GGC TCA GGA), and sequencing was performed using primer pMyc14 [5' G(A/G)G (A/G)TA CTC GAG TGG CGA AC] (2, 3). Sequencing analysis revealed Mycobacterium sherrisii; the 707-bp-long sequence showed 0 mismatches with a sequence of M. sherrisii (GenBank accession number AY353699) and 4 mismatches with sequences of M. simiae (GenBank accession number AY604042) and M. triplex (GenBank accession number U57632), respectively. A total of eight respiratory specimens over a period of 24 days (six sputum samples, two bronchial aspirates) were positive by culture, and sequence analysis revealed M. sherrisii in all cases. Six of these eight specimens showed acid-fast bacilli by microscopy. The Amplified M. tuberculosis Direct Test (Gen-Probe, San Diego, CA) was performed with three specimens; all tested negative. Upon identification, therapy was changed to clarithromycin, rifabutin, moxifloxacin, and sulfamethoxazole, according to the susceptibility pattern recently published (7). Pancytopenia attributed to sulfamethoxazole developed, and this medication was stopped. The drug susceptibilities were tested by the radiometric BACTEC 460TB (Becton Dickinson Microbiology Systems, Sparks, MD) method, and resistance (r) and susceptibility (s) values were determined for the following drugs (drug concentrations are given in micrograms per milliliter): amikacin (r, 1; s, 10); clarithromycin (r, 16; s, 32); ethambutol (s, 5); isoniazid (r, 1; s, 10); ofloxacin (r, 2; s, 20); rifabutin (r, 0.1; s, 1); and rifampin (r, 1; s, 10). Results for ciprofloxacin (r, 16; s, 32) were obtained by a broth microdilution method (5, 8).
Despite these results showing resistance or intermediate susceptibility in vitro for clarithromycin and rifabutin, the patient improved and therapy was left unchanged. At 16 weeks after initiation of combination antiretroviral therapy his CD4 cell count had risen from 19 to 53 cells/μl (11% of total lymphocytes) and HIV RNA levels had fallen from 595,000 to nondetectable levels. At the most recent follow-up, the patient was doing well.
Discussion. Mycobacteria other than M. tuberculosis (nontuberculous mycobacteria ) are mostly free-living organisms ubiquitous in the environment. In the immunocompetent patient, NTB occasionally cause disease, usually in patients with underlying pulmonary pathology. In the severely immunocompromised patient, such as in cases of advanced HIV disease, NTB infections can disseminate and result in considerable morbidity and mortality. Initiation of highly active antiretroviral therapy has led to an overall decline of NTB infections in HIV patients (4). The restoration of protective pathogen-specific immune responses is necessary to overcome NTB infections. These responses are sometimes immunopathological themselves and can cause disease, a phenomenon called immune reconstitution. In the time since immune reconstitution was recognized in HIV-infected patients undergoing potent antiretroviral combination therapy, numerous opportunistic infections have been associated with this phenomenon (1, 6). Often, opportunistic infections do not become manifest until after the initiation of combination antiretroviral therapy.
We report the first case of a pulmonary Mycobacterium sherrisii infection in an human immunodeficiency virus-infected patient. Our patient initially presented with no signs of inflammation. His cachexia was attributed to HIV wasting. Within 4 weeks of the initiation of antiretroviral combination therapy, he developed pulmonary symptoms associated with inflammation and fever. While the possibility cannot be excluded that he newly acquired M. sherrisii, it is likely that he had been previously colonized with this organism. We believe that he developed overt disease with immune reconstitution, which has been frequently associated with NTB (6).
M. sherrisii has been recently described as a putative new NTB (7). The initial report refers to the isolates used as clinical isolates, but no data about the type of sample or the clinical manifestations of the involved cases are given. Sequencing analysis of all eight positive cultures of independently recovered specimens yielded identical results, confirming species identification. The initial therapy was changed according to the only published susceptibility data. When our own susceptibility testing was available, the patient was left on the current regimen, despite testing resistant for part of the therapy. It is probable that the clinical improvement was related to both an increase in his CD4 cell count and the specific therapy for M. sherrisii.
In summary, we present the first patient with a pulmonary infection with M. sherrisii and HIV infection. In our case, infection with M. sherrisii became manifest during highly active antiretroviral therapy. M. sherrisii should be added to the list of NTB causing disease in advanced HIV infection.
ACKNOWLEDGMENTS
We thank K. Herzog and the technicians of the Institute of Medical Microbiology for excellent technical assistance. There was no conflict of interest or financial support for any author for this work.
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