Clinical significance of the isolation of rapidly growing mycobacteria

BACKGROUND: To assess the clinical significance of the isolates of rapid-growing mycobacteria in a Universitary hospital from Madrid (Spain). PATIENTS AND METHODS: Review of medical records from patients with isolates of rapid-growing mycobacteria identified between 1979 and 1996 in the Microbiology department of the Fundación Jiménèz Díaz (Madrid, Spain). RESULTS: Rapid-growing mycobacteria were isolated from 28 patients during the study period (13 M. chelonae, 10 M. fortuitum, 2 M. mucogenicum, 1 M. marinum, 1 M. smegmatis and 1 M. flavascens). Clinical records of 26 patients were reviewed, being the isolate significative in 10 cases (5 soft tissue infections, 2 peritonitis in patients undergoing Continuous Ambulatory Peritoneal Dialysis [CAPD], 1 urinary tract infection, 1 osteomyelitis and 1 catheter-related soft-tissue infection). No patient was HIV+. All infections cured except 2 of them (the urinary tract infection and the osteomyelitis). Catheter withdrawal was needed in 3 cases (peritonitis in CAPD and catheter-related soft-tissue infection), apart from proper antimicrobial therapy. CONCLUSION: The most frequent rapid-growing mycobacteria isolated were those of the M. fortuitum complex. In our experience, isolation of rapid-growing mycobacteria from skin and soft-tissue samples was usually clinically significant, while isolates from respiratory tract, gut and blood cultures are always nonsignificant.     

Possible involvement of catalase in the protective effect of interleukin-6 against 6-hydroxydopamine toxicity in PC12 cells

Records of patients have been retrospectively examined studied during an 11-y period, from whom Mycobacterium fortuitum or M. chelonae was isolated in Sweden. Respiratory isolates were obtained from 71 patients. Clinical information was accessible in 52, chest X-ray was pathological in 51, and 42 had underlying diseases. Four skin and 4 urine isolates were observed. Two cases of osteitis and 2 bone marrow isolates of M. chelonae were found. One girl had a submandibular lymph node abscess with M. fortuitum. Of 2 HIV patients, 1 had positive blood cultures with M. fortuitum and the other positive sputum culture with M. chelonae. The broad spectrum of infections with M. fortuitum complex necessitates an integrated judgement of clinical and bacteriological data to determine the relevance of such isolates.     

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.     

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.     

Studies on diurnal fluctuation and variation among days in the relative frequencies of the stages of the cycle of seminiferous epithelium in the mouse (author''s transl)]

The clinical records of 7 patients referred to the National Jewish Hospital and Research Center over a 6-year period for evaluation of an abnormal chest x-ray and repeated sputum isolates of rapidly growing mycobacteria (Runyon's Group IV) were reviewed to determine the potential pathogenicity of these organisms. Mycobacterium fortuitum was isolated from 5 patients and Mycobacterium chelonei from 2. Haemoptysis, cough and weight loss were prominent in 6. Three had rheumatoid arthritis. Although two demonstrated cutaneous anergy, lymphocyte responsiveness to PHA was normal. PPD-F was not useful in skin testing or in the in vitro evaluation of lymphocyte function. Histologic examination of the lungs of 2 patients demonstrated caseating granulomata. One patient died of massive pulmonary haemorrhage soon after intiation of therapy. Multi-drug treatment regimens generally resulted in progressive sterilization of the sutum and improvement in the appearance of the chest x-ray. We conclude that some rapidly growing mycobacteria can cause potentially fatal cavitary lung disease and that intensive anti-tuberculosis therapy may successfully alter its course.     

Non-tuberculous mycobacterial infection in children with cancer

Reported here is the clinical presentation and management of patients with rapidly growing non-tuberculous mycobacterial infection diagnosed in a paediatric oncology unit. A retrospective analysis that correlated patient isolates with the children's cancer registry revealed two cases of non-tuberculous mycobacterial infection; both had been observed within the last 6 years and were due to Mycobacterium chelonae. The first case was line-associated and the second was a disseminated infection. In both cases the patients were lymphopenic and had had indwelling vascular catheters. Neither patient was neutropenic. The literature on mycobacterial infection in children with cancer is also reviewed.     

Pseudo-outbreak of septicemia due to rapidly growing mycobacteria associated with extrinsic contamination of culture supplement

Between April and December 1994, 23 blood cultures from human immunodeficiency virus-infected patients grew rapidly growing mycobacteria suspected to be Mycobacterium chelonae at a hospital in New Jersey. The isolates were later identified as M. abscessus. Several bacterial species, including M. abscessus, were cultured from an opened multidose supplement vial (BBL Septi-Chek AFB Supplement) that had been used for mycobacterial blood cultures. The M. abscessus isolates from case patients and the supplement vial had identical multilocus enzyme electrophoresis and antimicrobial susceptibility patterns. Finding a contaminated vial of supplement, together with the lack of a distinct syndrome in case patients, was consistent with a pseudo-outbreak.     

Megaesophagus and pneumonia associated with Mycobacterium chelonei. A case report and a literature review

The case of a 37-year-old woman who developed a subacute, bilateral, noncavitary pneumonia 5 years after a colon interposition esophagoplasty is presented. Mycobacterium chelonei, subspecies abscessus, was assigned a pathogenic role based on the findings of (1) a clinical and roentgenographic picture consistent with tuberculosis, (2) sputum smears showing acid-fast bacilli, (3) repeated sputum cultures yielding heavy growths of Mycobacterium chelonei, subspecies abscessus, and (4) a 12-mm by 12 mm-skin test response to homologous antigen (purified protein derivative-CL) with no response to an equivalent dose of purified protein derivative-S. The patient recovered fully without significant antituberculous chemotherapy. A survey of the literature revealed 11 similar case reports featuring a documented association between megaesophagus and pulmonary infection with rapidly growing mycobacteria.     

Identification of mycobacteria infecting fish to the species level using polymerase chain reaction and restriction enzyme analysis

An assay is described utilizing PCR technology for a rapid diagnostic test to identify fish infection with Mycobacterium marinum, M. fortuitum and M. chelonae. A 924 bp DNA fragment from a highly conserved area of the mycobacterial 16S rRNA gene was amplified using mycobacteria genus-specific primers and digested with restriction enzymes (BanI and ApaI). This examination yielded unique restriction patterns for each mycobacterial specie enabling identification of mycobacteria infecting fish to the species level. The protocol can be applied to purified DNA, a simple colony preparation or infected fish tissue. This protocol can be completed in 1-2 days.     

Failure to recognize rapidly growing mycobacteria in a proficiency testing sample without specific request--a wider diagnostic problem?

Fifty participants in the Swiss External Quality Control Program in Bacteriology/Mycology received a diagnostic sample containing Mycobacterium fortuitum. Only 31 used some sort of acid-fast stains, and 13 reported the diagnosis of M. fortuitum or rapidly growing mycobacteria. We conclude that the presence of 'rapid growers' in routine bacteriology samples is underestimated, and that acid-fast stains should be performed on suspicious Gram-positive rods.     

Variables affecting results of sodium chloride tolerance test for identification of rapidly growing mycobacteria

The sodium chloride tolerance test is often used in the identification of rapidly growing mycobacteria, particularly for distinguishing between Mycobacterium abscessus and Mycobacterium chelonae. This test, however, is frequently unreliable for the identification of some species. In this study we examined the following variables: medium manufacturer, inoculum concentration, and atmosphere and temperature of incubation. Results show that reliability is improved if the test and control slants are inoculated with an organism suspension spectrophotometrically equal to a 1 McFarland standard. Slants should be incubated at 35 degrees C in ambient air and checked weekly for 4 weeks. Growth on control slants should be critically evaluated to determine the adequacy of the inoculum; colonies should number greater than 50. Salt-containing media should be examined carefully to detect pinpoint or tiny colonies, and colonies should number greater than 50 for a positive reaction. Concurrent use of a citrate slant may be helpful for distinguishing between M. abscessus and M. chelonae. Molecular methodologies are probably the most reliable means for the identification of rapidly growing mycobacteria and should be used, if possible, when unequivocal species identification is of particular importance.     

Breast cancer five-year survival, by New South Wales regions, 1980 to 1991

Mycobacterium xenopi is one of the most frequently isolated nontuberculous mycobacteria in Ontario, Canada. We reviewed the records of 28 human immunodeficiency virus (HIV)-infected patients from whom M. xenopi was isolated between 1982 and 1995. M. xenopi was recovered from respiratory specimens from 24 patients, most of whom had clinical and radiographic evidence of pulmonary disease. However, coexistent pulmonary infection due to other pathogens was found in 17 patients: Pneumocystis carinii (9 patients), cytomegalovirus (5), Haemophilus influenzae (2), Mycobacterium avium complex (2), Streptococcus pneumoniae (1), Staphylococcus aureus (1), Aspergillus species (1), and Histoplasma capsulatum (1). Three patients had bacteremia with M. xenopi, including two patients with pulmonary infection. Two of the bacteremic patients had chronic fever and a wasting syndrome. Twenty-one (75%) of the 28 patients were thought to be colonized, and seven patients (25%; of whom four had CD4 cell counts of < or = 50/mm3) were thought to have significant infection due to M. xenopi. Sixteen patients died, but in no case was death attributable to M. xenopi infection. In a region where M. xenopi is a relatively common mycobacterial isolate, the organism frequently colonizes HIV-infected patients. Significant disease occurs in those patients with more advanced HIV infection.     

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.     

Bacteriology of mycobacteria: taxonomic and morphological characteristics

Bacteriological characteristics of organisms belonging to Genus Mycobacterium which involves more than 60 species are described. Mycobacterial organisms can be divided into the following groups having differential characteristics, on the basis of the results of biological, biochemical, and genetic investigations, including lipid analysis, DNA probe test, and comparative 16S ribosomal RNA sequencing. First, Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis, M. africanum, etc.). Second, cultivable but slowly growing nontuberculous mycobacteria, including photochromogens (Runyon Group I) such as M. kansasii, M. marinum, M. simiae, M. intermedium, and M. asiaticum, scotochromogens (Runyon Group II) such as M. scrofulaceum, M. szulgai, M. injectum, M. lentiflavum, and M. gordonae, nonphotochromogenens (Runyon Group III) such as M. avium, M. intracellulare, M. xenopi, M. malmoense, M. genavense, M. celatum, and M. gastri. Third, cultivable rapidly growing nontuberculous mycobacteria (Runyon Group IV) including M. fortuitum, M. chenolae, M. abscessus, M. phlei, and M. smegmatis. Fourth, noncultivable mycobacteria including M. leprae. About 30 species of Mycobacterium cause pulmonary, dermal, lymphatic, and disseminated infections in human beings. This paper mainly deals with the taxonomic, morphological, and other biological characteristics of these mycobacterial organisms.     

Nontuberculous mycobacterial infection of the central nervous system in patients with AIDS

Infections due to nontuberculous mycobacteria (NTM) are especially common in patients with AIDS. Meningitis due to NTM, however, is rare. A search for CSF cultures positive for NTM over the past 11 years at our hospital yielded 16 cases. Of these, 15 were caused by Mycobacterium avium-intracellular (MAI), and one was caused by M fortuitum. All patients with MAI infection had widespread dissemination and at least one risk factor for AIDS. Clinical features included weight loss, altered mentation, and seizures. Analysis of cerebrospinal fluid revealed a mildly elevated leukocyte count with lymphocyte predominance and normal protein and glucose values. All direct smears were negative for acid-fast bacilli. In-hospital mortality was 67%. The patient with infection due to M fortuitum had a preexisting diagnosis of AIDS and had a right upper lobe pneumonia and headaches. Cranial CT showed an enlarged infundibulum of the pituitary gland. Results of CSF analysis were essentially normal, and direct smears were negative. He left the hospital against medical advice. Our study indicates that the finding of MAI in the CSF in patients with AIDS is associated with an in-house mortality of 67% indicating a very poor prognosis.     

Epidemiology of disease caused by nontuberculous mycobacteria

The clinically important nontuberculous mycobacteria include M. kansasii, M. genavense, M. marinum, M. simiae, M. scrofulaceum and M. szulgai, M. avium, M. haemophilum, M. intracellulare, M. malmoense, M. ulcerans, and M. xenopi, M. abscessus, M. chelonae, M. fortuitum, and (rarely) M. smegmatis. Four clinical syndromes account for nearly all cases: pulmonary disease, lymphadenitis, skin or soft tissue disease, and disseminated disease in AIDS. M. avium and M. intracellulare (known together as M. avium complex), are the most common causes of pulmonary disease, lymphadenitis, and disseminated disease. All four clinical syndromes seem to be increasing in frequency, particularly in immunosuppressed hosts. Nontuberculous mycobacteria are acquired from the environment, but specific reservoirs of these organisms leading to human disease have not been defined.     

Mycobacterium fortuitum mastoiditis

Improved techniques of bacteriologic identification have led to increasing recognition of the clinical significance of the atypical or anomymous mycobacteria. Mycobacterium fortuitum, included in group IV of Runyon's classification because of its characteristic rapid growth, is widespread in nature as a saprophyte. Its facultative pathogenicity has received increasing attention in the literature recently with reports of a number of isolated infections, epidemics, and deaths. We report a case of mastoiditis due to M fortuitum and discuss the pathogenesis and treatment. This is the first known report of the organism causing otolaryngologic disease.     

katGI and katGII encode two different catalases-peroxidases in Mycobacterium fortuitum

It has been suggested that catalase-peroxidase plays an important role in several aspects of mycobacterial metabolism and is a virulence factor in the main pathogenic mycobacteria. In this investigation, we studied genes encoding for this protein in the fast-growing opportunistic pathogen Mycobacterium fortuitum. Nucleotide sequences of two different catalase-peroxidase genes (katGI and katGII) of M. fortuitum are described. They show only 64% homology at the nucleotide level and 55% identity at the amino acid level, and they are more similar to catalases-peroxidases from different bacteria, including mycobacteria, than to each other. Both proteins were found to be expressed in actively growing M. fortuitum, and both could also be expressed when transformed into Escherichia coli and M. aurum. We detected the presence of a copy of IS6100 in the neighboring region of a katG gene in the M. fortuitum strain in which this element was identified (strain FC1). The influence of each katG gene on isoniazid (isonicotinic acid hydrazide; INH) susceptibility of mycobacteria was checked by using the INH-sensitive M. aurum as the host. Resistance to INH was induced when katGI was transformed into INH-sensitive M. aurum, suggesting that this enzyme contributes to the natural resistance of M. fortuitum to the drug. This is the first report showing two different genes encoding same enzyme activity which are actively expressed within the same mycobacterial strain.     

Mediastinitis due to Mycobacterium fortuitum infection following Fontan operation in a child

Here we report a case of mediastinitis due to Mycobacterium fortuitum infection in a child after a Fontan operation. To our knowledge this is the first report of atypical mycobacterial mediastinal infection after congenital heart surgery. Atypical mycobacteria can be the cause of "culture negative" sternal and thoracotomy wound infections. A brief review of the literature is included in the discussion.     

Mycobacterium novocastrense sp. nov., a rapidly growing photochromogenic mycobacterium

A strain isolated from a biopsy sample taken from a slowly spreading skin granulation on a child's hand was found to have properties consistent with its classification in the genus Mycobacterium. An almost complete gene sequence of the 16S rRNA of the strain was determined following the cloning and sequencing of the amplified gene. The sequence was aligned with those available for mycobacteria, and phylogenetic trees were inferred with four tree-making algorithms. The organism, which formed a distinct phyletic line within the evolutionary radiation occupied by rapidly growing mycobacteria, was readily distinguished from members of validly described species of rapidly growing mycobacteria on the basis of its mycolic acid pattern and a number of other phenotypic features, notably its ability to form yellow pigmented colonies when incubated in the light. The name proposed for this new species is Mycobacterium novocastrense. The type strain is DSM 44203.