Disease caused by Mycobacterium kansasii in patients with HIV infection

BACKGROUND: To describe the clinical features and response to therapy in Mycobacterium kansasii disease among HIV infected patients, an increasing problem in our setting. METHODS: A retrospective survey of all charts from patients with HIV infection with Mycobacterium kansasii infection recorded between April 1985 and December 1991. RESULTS: A total of 13 patients were identified. All of them had clinically significant respiratory tract samples with a definite M. kansasii isolation. Only three had disseminated disease. In all but two cases, CD4 cell count at diagnosis time was lower than 200/mm3. Chest X-ray films showed interstitial pattern (8 cases) or alveolar condensation (3 cases) and lung cavities were seen in 4 patients. All patients with lung disease and one with disseminated disease responded well to anti-tuberculous therapy. CONCLUSION: Mycobacterium kansasii produces disease in advances stages of HIV-induced immunosuppression. The most common primary location is pulmonary, but disseminated forms can also be seen. The infection can be controlled with standard anti-tuberculous therapy.     

Nontuberculous mycobacterial infections

The acquired immunodeficiency syndrome (AIDS) pandemic has led to greater understanding and respect for the pathogenic potential of non-tuberculous mycobacteria. Mycobacterium avium complex (MAC) has emerged as the most common systemic bacterial infection in AIDS, causing debilitating disseminated disease in late-stage HIV-infected patients. With the release of the macrolide antibiotics, clarithromycin and azithromycin, effective and well-tolerated therapeutic regimens for MAC have been developed which prolong survival and increase quality of life. The macrolides and rifabutin are also effective as preventive therapy for MAC in patients with AIDS. Mycobacterium kansasii, which causes pulmonary disease similar to tuberculosis as well as disseminated disease in AIDS, is treatable with isoniazid, rifampin and ethambutol. Clinical syndromes and therapeutic options for other non-tuberculous mycobacteria in AIDS are also reviewed.     

Randomized, open-label trial of azithromycin plus ethambutol vs. clarithromycin plus ethambutol as therapy for Mycobacterium avium complex bacteremia in patients with human immunodeficiency virus infection. Veterans Affairs HIV Research Consortium

Disseminated Mycobacterium avium complex (MAC) infection continues to be a common opportunistic infection in patients infected with human immunodeficiency virus (HIV). The optimal therapy for disseminated MAC infection is unclear. We compared azithromycin plus ethambutol with clarithromycin plus ethambutol in the treatment of disseminated MAC infection in HIV type 1-infected patients, examining the frequency of bacteremia clearance, time to clearance, and study drug tolerance after 16 weeks of therapy. Fifty-nine patients for whom blood cultures were positive for MAC were enrolled in the study from 10 university-affiliated Veterans Affairs Medical Centers. Thirty-seven patients were evaluable for determination of quantitative bacteremia and clinical outcomes. Clearance of bacteremia was seen at the final visit in 37.5% of azithromycin-treated patients and in 85.7% of clarithromycin-treated patients (P = .007). The estimated median time to clearance of bacteremia was also significantly different between the two treatment arms: 4.38 weeks for clarithromycin recipients vs. > 16 weeks for azithromycin recipients (P = .0018). Only one isolate developed macrolide resistance during therapy. Abatement of symptoms, other laboratory-evident abnormalities, and adverse effects were similar in the two groups. At the doses used in this study, clarithromycin/ethambutol produced a more rapid resolution of bacteremia than did azithromycin/ethambutol, and clarithromycin/ethambutol was more effective at sterilization of blood cultures after 16 weeks of therapy.     

A case of AIDS with disseminated Mycobacterium kansasii infection in which Mycobacterium, avium complex was also detected from his sputum repeatedly

A 43 year-old Japanese male was admitted to our hospital because of productive cough and fever. He was diagnosed as acquired immunodeficiency syndrome (AIDS) in 1994. Laboratory findings were as follows: WBC was 3200/microliter, CD4+ T lymphocyte count was 22/microliter. His chest X-ray film taken on admission showed infiltration with small cavity lesion in middle left lung field. Tuberculin skin reaction was negative. He was treated with isoniazid 0.4 g, rifampicin 0.45 g, and ethambutol 0.75 g each daily. Sputum smear was positive for acid fast bacilli. The cultured isolates were identified as Mycobacterium kansasii (M. kansasii) and Mycobacterium avium complex (MAC). Urine smear was also positive for acid fast bacilli. The cultured isolates were identified as M. kansasii. He was diagnosed as disseminated M. kansasii infection and suspected MAC infection. About one hundred days later, his chest X-ray film showed reticular shadow. His clinical symptoms improved and the sputum smear and culture converted to negative for acid fast bacilli. Based on these findings, his MAC discharge was considered not as MAC infection, but MAC colonization. He returned to the former hospital for AIDS treatment, and he died in August 1996.     

Unilateral adrenal mass due to Mycobacterium kansasii in an AIDS patient

Infection with Mycobacterium kansasii in patients with acquired immunodeficiency syndrome usually involves the lung or disseminated infection. We report a case of infection with M kansasii confined to the adrenal gland and possibly to an adjacent vertebral body that presented as a fever of undetermined origin.     

Thirteen bovine microsatellite markers that are polymorphic in sheep

Macrolide resistance in disseminated Mycobacterium avium infection is of major concern in AIDS patients as these drugs represent the main component of combination therapy. Clarithromycin and azithromycin should not be used alone for the treatment and prophylaxis of the disease because of the risk of selecting resistant strains. We report the case of a clarithromycin resistant disseminated M. avium infection in an AIDS patient, acquired after long term monotherapy with clarithromycin for the treatment of cryptosporidiosis.     

Paranasal sinus infection due to atypical mycobacteria in two patients with AIDS

Atypical mycobacteria, which are common opportunistic pathogens in patients with AIDS, have not been previously implicated in the pathogenesis of paranasal sinus infections; we describe two such patients. Clinical and radiographic evidence of bilateral maxillary and ethmoid sinusitis was observed for one patient; his infection proved resistant to therapy with conventional antimicrobials and decongestants. Endoscopic ethmoid sinus biopsy yielded a specimen containing acid-fast bacilli (AFB) that were later identified as Mycobacterium kansasii. Antimycobacterial therapy had not resulted in amelioration of the sinusitis > 2 months later, at which time he died of cerebral toxoplasmosis. The second patient presented with a tender right frontotemporal soft-tissue mass; a computed tomogram disclosed that it extended through the frontal bone to the frontal sinus. Inflamed tissue debrided from the sinus contained AFB; cultures first yielded M. kansasii and later Mycobacterium avium complex. Bacteremia due to both organisms was also demonstrated. Infection progressed despite therapy.     

Helicobacter pylori and gastric malignancies

Osteolytic lesions of the skull are an unusual complication in patients with AIDS. We report a case of multiple cranial abscesses as the major manifestation of a disseminated infection due to Mycobacterium kansasii in a patient with AIDS.     

Infections due to nontuberculous mycobacteria in children with leukemia

We reviewed the spectrum of infections due to nontuberculous mycobacteria (NTM) in children with leukemia. Three children acquired such infections. One patient developed pneumonia after the cessation of chemotherapy when Mycobacterium xenopi was identified in his lung biopsy specimen. He required 2 years of treatment with antituberculous agents and clarithromycin. Cultures of central and peripheral blood specimens from two patients yielded Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Broviac catheters were likely the source of infection. Removal of the catheters and antibiotic treatment resulted in cure. Central venous catheters in leukemic children are potential sources of infection. For febrile neutropenic children with leukemia who do not respond to antibiotic therapy, cultures positive for diphtheroids or negative routine bacterial and fungal cultures should raise a suspicion for infections due to NTM. Systemic infections may require up to 2 years of therapy. Removal of the infected catheters during persistent or recurrent infections in necessary for control of the infection.     

Clinicopathological study of cases with Mycobacterium szulgai infection

Pulmonary mycobacteriosis is usually caused by Mycobacterium tuberculosis, Mycobacterium avium complex, or Mycobacterium kansasii. There are, however, other slow-growing mycobacteria which can cause pulmonary infection. Mycobacterium szulgai, first reported in 1972, is a scotochromogenic species which can affect human lungs, although human-to-human spread of infection is thought to be unlikely. We have recently treated three cases of middle-aged to elderly persons (45-87 year-old), two of them had underlying diseases (one with intrapulmonary and the other with extrapulmonary). All patients had constitutional symptoms (cough, sputum, dyspnea), and chest roentgenograms demonstrated either cavitation with scattered nodules or peripheral infiltrates predominantly in upper lobes, resembling pulmonary tuberculosis. In two cases, M. szulgai was identified by using DNA-DNA hybridization method. The in vitro susceptibility of M. szulgai to antimycobacterial drugs was better than that of M. avium complex, and it was resistant only to paraaminosalicylate, cycloserine, and partially to isoniazid. Pulmonary disease of three patients were successfully treated with a combination of multiple antimycobacterial agents including rifampin, ethambutol, isoniazid, or streptomycin.     

Use of microscopic morphology in smears prepared from radiometric cultures for presumptive identification of Mycobacterium tuberculosis complex, Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi

The aim of this study was to assess the feasibility of a method for presumptive identification of mycobacteria, based on the morphology in smears prepared from radiometric Bactec-positive cultures (Becton Dickinson, USA) and to select the appropriate DNA probe (AccuProbe; Gen Probe, USA). The smear morphology of acid-fast bacilli was evaluated in 468 positive cultures from clinical samples: 313 Mycobacterium tuberculosis complex, 67 Mycobacterium avium complex, 32 Mycobacterium kansasii, 49 Mycobacterium xenopi, and seven Mycobacterium gordonae. The sensitivity and specificity for various morphological patterns were as follows: cord formation for Mycobacterium tuberculosis complex 90% and 100%, respectively; striped bacilli for Mycobacterium kansasii, 66% and 99%; sea urchin for Mycobacterium xenopi, 96% and 99%; short bacilli for Mycobacterium avium complex, 61% and 99%; fine-striped bacilli associated with Mycobacterium avium complex from blood samples, 33% and 98%. This criterion was applied in the selection of a suitable DNA probe for the identification of 178 cultures. The correct probe was selected in 98%, 97%, and 72% of cultures, respectively, for Mycobacterium tuberculosis complex, Mycobacterium avium complex, and Mycobacterium kansasii. The observation of acid-fast bacilli morphology in radiometric cultures is a rapid and cost-efficient method for presumptive identification of common clinical isolates of mycobacteria.     

Efficacy of serial electrical cardioversion therapy in patients with chronic atrial fibrillation after valve replacement and implications for surgery to cure atrial fibrillation

In April 1993, a 51-year-old woman had a fever, and an infiltrative shadow was seen in the left upper lobe on a chest X-ray film. Repeated sputum cultures were positive for Mycobacterium avium complex. She underwent antituberculosis therapy consisting of pyrazinamide, ofloxacin, and streptomycin. Her symptom disappeared and the abnormal shadow resolved. In January 1994, she was admitted to the hospital because of bloody sputum and abnormal chest X-ray findings consisting of a left hilar mass and atelectasis of the left upper lobe. Bronchoscopy revealed multiple polypoid lesions without necrosis in the left upper-lobe bronchus. Histological examination showed that the tumor consisted of an aggregation of lymphocytes and plasma cells, and was positive for Ziehl-Neelsen stain. The acid-fast bacillus was identified as Mycobacterium avium by the DNA probe method. Anti-tuberculosis treatment was given: rifampicin, isoniazid, sparfloxacin, and clarithromycin. Three months later, the atelectasis and the polypoid mass in the left upper-lobe bronchus had disappeared. We believe that the polypoid lesions in the left upper-lobe bronchus were due to infection by Mycobacterium avium. The patient was HIV-negative and immunocompetent. Such endobronchial lesions caused by Mycobacterium avium are rare in HIV-negative hosts.     

Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient

Mycobacterium chelonae (formerly known as M. chelonae subspecies chelonae) is a rapidly growing mycobacterium that can cause disseminated infections, especially in immunocompromised hosts. The bacterium is typically resistant to antimicrobial agents; less than 20% of M. chelonae isolates are susceptible to trimethoprim-sulfamethoxazole, doxycycline, erythromycin, or ciprofloxacin. Findings in a recent study suggested that clarithromycin may be the drug of choice for the treatment of cutaneous (disseminated) disease due to M. chelonae. We describe a 60-year-old heart transplant patient with disseminated M. chelonae infection for whom monotherapy with clarithromycin failed because of the rapid development of resistance to the drug.     

Detection of Mycobacterium tuberculosis DNA in lobular granulomatous panniculitis (erythema induratum-nodular vasculitis)

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.     

Clinicopathologic implications of MDM2, p53 and K-ras gene alterations in osteosarcomas: MDM2 amplification and p53 mutations found in progressive tumors

The role of rapidly growing mycobacteria in the pathogenesis of pulmonary disease is being increasingly recognized; however, the clinical significance of these mycobacteria in patients with underlying malignancy has not been well studied. Over a 6-year period, 37 cancer patients with rapidly growing mycobacteria isolated from respiratory specimens were identified at our center. Mycobacterium chelonae group was isolated in 24 cases and Mycobacterium fortuitum in 13 cases. Of the 24 cases with cultures yielding Mycobacterium chelonae group, eight met the study criteria for infection and were determined to be clinically significant, whereas only one of the Mycobacterium fortuitum isolates was determined to represent infection. An average of two antimicrobial agents were used for treatment, most commonly clarithromycin, ciprofloxacin, and trimethoprim/sulfamethoxazole. Although the isolation of rapidly growing mycobacteria represents colonization in most cases, these bacteria, especially the Mycobacterium chelonae group, may cause pulmonary disease in cancer patients. The clinical and radiological findings are usually non-specific in this population, and patients with respiratory cultures yielding rapidly growing mycobacteria should be assessed carefully to distinguish infection from colonization. Effective therapy can be provided with oral regimens that include at least two antibiotics to which the organism is susceptible.     

Mycobacterium fortuitum infection of the sternum. Review of the literature and case illustration

Sternal wound infection with atypical mycobacteria following open heart surgery is a rare occurrence. Previous reports have described infection by Mycobacterium fortuitum, an acid-fast bacillus and member of a larger family of rapidly growing mycobacteria. The source and mode of transmission have not been identified. Surgical debridement and the combination of aminoglycosides and quinolones have been shown to be effective methods of treatment. More recently, clarithromycin has been shown to be the drug of choice against rapidly growing mycobacteria. We describe a 49-year-old woman who underwent infundibular stenosis repair and in whom M fortuitum sternal osteomyelitis developed. Total sternectomy, muscle flap reconstruction, and antibiotic treatment successfully eradicated the infection.     

Nontuberculous mycobacteriosis as a complication of the Swyer-James syndrome

The chest radiograph of a 35-year-old man with fatigue, exertional dyspnoea and haemoptyses revealed a cavity in the left upper lobe and a shrunken left lung with radiolucency greater than that on the right. Acid-fast rods in sputum were identified as Mycobacterium kansasii on culture. Scintigraphy showed a 9% residual perfusion on the left and abnormal ventilation, compatible with Swyer-James syndrome. This had favoured the development of a mycobacterial infection. There was also a decrease in ciliary function (rate of 4-7 Hz, normal: 10-11). Treatment, begun when tuberculosis had been suspected, was after sensitivity tests changed to a combination of rifampicin (600 mg), ethambutol (1600 mg) and protionamide (500 mg) daily. There was marked regression of the findings within 4 weeks, but treatment was prematurely stopped after 11 months. Two years later there was a recurrence which again responded well to the same drug regimen with additional sulphamethoxazole (1600 mg/d).     

Reduced nociceptive behavior in islet amyloid polypeptide (amylin) knockout mice

Macrolide resistance is an emerging problem in AIDS patients who receive these agents for treatment or prophylaxis against Mycobacterium avium (MAC) infection. We compared the emergence of resistant MAC strains during therapy with clarithromycin (clarithromycin resistance was defined as MIC > or = 32 microg/ml) and azithromycin (azithromycin resistance was defined as MIC > or = 128 microg/ml) in C57BL/6 beige mice. Treatment with clarithromycin and azithromycin resulted in a decrease of 98.5% in the number of viable bacteria in spleens at week 8 and 99% at week 12 compared with the number of bacteria present in spleen before the initiation of therapy (P < 0.001). Splenic homogenates were also plated onto 7H11 agar plus clarithromycin at 32 microg/ml or azithromycin at 128 microg/ml. Resistance emerged significantly more often in mice treated with clarithromycin (100% of treated mice at both 8 and 12 weeks) than in those receiving azithromycin (0% at week 8 and 14% at week 12). The frequencies of resistance of the MAC population in the spleen to clarithromycin were 2.1 x 10(-3) at week 8 and 1.1 x 10(-2) at week 12, whereas resistance to azithromycin was absent at week 8 (all mice) and was approximately 3.5 x 10(-5) (mean for the three positive animals) at week 12. Clarithromycin was more effective in initial reduction of MAC burden in tissue after 8 and 12 weeks of treatment, but resistant strains emerged significantly more frequently after treatment with clarithromycin than after treatment with azithromycin.     

Long-term outcomes of treatment of Mycobacterium avium complex bacteremia using a clarithromycin-containing regimen

OBJECTIVES: To describe the long-term outcomes of treatment of AIDS-related Mycobacterium avium complex (MAC) bacteremia using a standard clarithromycin-based regimen. DESIGN: Retrospective study of patients with MAC bacteremia diagnosed between April 1992 and April 1995. SETTING: An urban AIDS clinic SUBJECTS: One hundred seventy-six consecutive patients with MAC bacteremia. INTERVENTIONS: Clarithromycin 500 mg twice daily, ethambutol 800 or 1200 mg daily, and clofazimine 100 mg daily. MAIN OUTCOME MEASURES: Late treatment failure (defined as a positive blood culture more than 90 days after starting treatment), clarithromycin susceptibility of initial and treatment-failure isolates, DNA fingerprinting of isolates from treatment failures. RESULTS: Two out of 176 (1.1%) baseline isolates were resistant to clarithromycin. One hundred and fifty-one patients were treated for MAC bacteremia, 144 (95%) with the standard regimen. Of the 117 patients who survived > 90 days after starting therapy, 25 (21%) met the criteria for late treatment failure. Of the 22 treatment-failure isolates available for susceptibility testing, 19 (86%) were resistant to clarithromycin. Therefore, 13% of patients treated using the standard regimen (19 out of 144) had treatment failure associated with the emergence of clarithromycin resistance. Using logistic regression, non-compliance was associated with treatment failure (P = 0.02). Fourteen out of the 17 (82%) evaluable paired isolates had identical DNA fingerprint patterns, whereas three pairs showed that a different strain of MAC was present at the time of treatment failure. CONCLUSIONS: Initial resistance to clarithromycin was rare during this period. However, late treatment failure associated with the emergence of clarithromycin resistance was relatively common during long-term follow-up. Most late treatment failures represented emergence of clarithromycin resistance in the initial strain.     

Developmental toxicity of 4-substituted amphetamines in mice

Until recently, therapy for most Nontuberculous Mycobacterial (NTM) disease, especially disease caused by Mycobacterium avium-complex (MAC), has been difficult and frustrating. The introduction of the newer macrolides (clarithromycin and azithromycin) has significantly added to the efficacy of regimens for both disseminated and pulmonary MAC disease. Clinical activity of these agents is lost when a MAC isolate develops in-vitro resistance that is facilitated by use of the macrolides as single agents. These valuable drugs should, therefore, never be used as single agents for the treatment of disseminated or pulmonary MAC disease. The newer macrolides also show promise for the treatment of other NTM infections such as those caused by M. abscessus, M. fortuitum, M. chelonae, M. xenopi, M. marinum, M. haemophilum, and M. genavense. Rifabutin, a derivative of rifamycin S, is an effective agent for prophylaxis against disseminated MAC and may have utility for treatment of pulmonary and disseminated MAC disease. Interactions between clarithromycin and rifamycin may alter efficacy of the macrolide and enhance toxicity of rifabutin. Although therapy of many NTM infections remains difficult with somewhat unpredictable results, the introduction of newer drugs, particularly the macrolides, has appreciably improved a previously dismal outlook for successful therapy.