Linezolid-induced lactic acidosis in two liver transplant patients with the mitochondrial DNA A2706G polymorphism.

Mitochondrial toxicity has been recently suggested to be the underlying mechanism of long-term linezolid-associated toxicity in patients with 16S rRNA genetic polymorphisms. Here, we report for the first time two cases of lactic acidosis due to long-term linezolid exposure in liver transplant recipients who presented an A2706G mitochondrial DNA polymorphism.

Nocardial brain abscess.

Nocardial infections, although rare, are challenging for clinicians to treat. The associated mortality rate remains high; such infections usually occur in immunocompromised patients who have predisposing factors such as malignancy, diabetes mellitus, malnutrition and uremia. However, there have been increasing reports of nocardial infections being observed in immunocompetent patients. Nocardial organisms are mostly isolated from plants and soil, and infection occurs most often as a result of inhalation or direct skin inoculation. Nocardial infections disseminate hematogenously from the primary location to distant end organs, including the brain, kidneys, joints and eyes. Sulfonamides are the drug of choice, based on empirical data. Given the high rate of relapse and the characteristic resistance pattern, treatment should be aggressive and continued for months, with antibiotic treatment being adjusted according to the drug sensitivity test. In our institution, there have been three documented patients with a nocardial brain abscess. All patients were treated with surgical evacuation followed by antibiotics. Here, we report on one patient and review the literature.

Nocardia cyriacigeorgica, an emerging pathogen in the United States.

Nocardia cyriacigeorgica is recognized as an emerging pathogen in many parts of the world. We present the first case description of invasive N. cyriacigeorgica pulmonary infection in the United States identified to the species level by 16S rRNA and hsp65 sequence analysis. A subsequent retrospective molecular screening of recent Nocardia clinical isolates at our New York City medical center yielded an additional six N. cyriacigeorgica isolates. Because routine laboratory algorithms for the phenotypic identification of Nocardia species are limited in practice, the true prevalence of N. cyriacigeorgica infections may be greater than currently appreciated. Indeed, we present evidence confirming that N. cyriacigeorgica is coincident with the unofficial species designation Nocardia asteroides complex antimicrobial susceptibility pattern type VI and distinct from the N. asteroides sensu stricto strain ATCC 19247(T). As nocardial species identity can predict antimicrobial susceptibility and guide clinical management, we offer simplified phenotypic and molecular protocols to assist the identification of N. cyriacigeorgica.

Nocardiosis in a tertiary care hospital in North India and review of patients reported from India.

Nocardiosis, an uncommon infection of the past, is being increasingly reported in recent years with rise of immunosuppressed patients. In India, very few centers have reported this disease. The present report describes twelve consecutive cases of nocardiosis reported over a period of 26 months (January 2004 to March 2006) from a tertiary care center in north India. The patients were predominantly males (75%) with age range of 8-65 years and mean age of 38.4 years. Eleven patients had known underlying illness including renal transplantation, human immunodeficiency virus infection, and long-term steroid therapy. One patient with cerebral nocardiosis had no detectable predisposing factor. Infection involved central nervous system (3 cases), lungs (5 cases), subcutaneous tissue (1 case), and anterior mediastinum (1 case). Disseminated infection was documented in two patients. Nocardia asteroides complex was incriminated in six patients, N. brasiliensis in five and N. otitidiscaviarum in one patient. All the isolates were sensitive to co-trimoxazole, amikacin, cefotaxime and imipenem. Good therapeutic response was observed in 10 (90.9%) of 11 patients treated with antibiotics including co-trimaxazole, cephalosporins, amikacin, and imipenem alone or in combination. The series of nocardiosis reported from India has also been reviewed.

Comparative evaluation of the in vitro antimycobacterial activities of six aminoglycoside antibiotics using an agar dilution method.

Given the increasing prevalence of mycobacterial resistance to aminoglycoside antibiotics, we examined the susceptibility of 76 clinical isolates of mycobacteria to arbekacin, amikacin, gentamicin, kanamycin, tobramycin and streptomycin using an agar dilution method. Only arbekacin and amikacin showed excellent therapeutic potential (minimum inhibitory concentrationis (MICs) < or =0.25-4 microg/ml) against 30 isolates of rapidly growing mycobacteria, including Mycobacterium fortuitum, M. chelonae and a related organism, Nocardia asteroides. The MIC(90)of tobramycin against 23 isolates of M. avium complex was 8 microg/ml, while that of the other 5 aminoglycosides ranged from 64-256 microg/ml. Of the 23 M. tuberculosis isolates tested, 5 showed aminoglycoside resistance (MICs 128 to > or =1,024 microg/ml), while the others were variably susceptible (MICs < or =0.25-32 microg/ml) to all 6 aminoglycosides. The chemotherapeutic potential of arbekacin, amikacin and streptomycin as treatment of tuberculosis was apparent; however, proper patient management would be required to control against the emergence of the drug-resistant strains during prolonged treatment.

Case report: Nocardia asteroides mycetoma.

Primary cutaneous infections with Nocardia asteroides are rare and have been reported in immunocompromised patients. Herein, we report a case of primary cutaneous Nocardia asteroides mycetoma of the skin in an immunocompetent individual. The infection was treated successfully with trimethoprim-sulfamethoxazole. Because a prolonged incubation time is required for the cultures and since additional biochemical tests are necessary for identification of this species, the clinician should alert the microbiology laboratory when such an infection is suspected clinically.

Reactive cutaneous cytophagocytosis in nocardiosis.

Cutaneous nocardiosis, which usually manifests in the form of pustules, abscesses, or subcutaneous nodules, is occasionally found in immunocompromised patients. A 59-yr-old Korean man with myasthenia gravis and thymoma developed nodular skin lesions on his trunk. Histopathologically, abscess formation with a dense infiltrate of neutrophils and many cytophagic histiocytes were observed. Numerous filamentous organisms, which turned out to be Nocardia asteroides by culture, were also found. After sulfamethoxazole-trimethoprim therapy, all of the skin lesions rapidly decreased in size, with a marked diminution of the number of cytophagic histiocytes, and cleared up within four months. On reporting a case of cutaneous nocardiosis showing unusual histopathologic findings, we considered that reactive conditions should be included in the differential diagnosis of the cutaneous cytophagocytosis, and that nocardiosis could be one of the diseases showing reactive cytophagocytosis.

Reactive Cutaneous Cytophagocytosis in Nocardiosis

Cutaneous nocardiosis, which usually manifests in the form of pustules, abscesses, or subcutaneous nodules, is occasionally found in immunocompromised patients. A 59-yr-old Korean man with myasthenia gravis and thymoma developed nodular skin lesions on his trunk. Histopathologically, abscess formation with a dense infiltrate of neutrophils and many cytophagic histiocytes were observed. Numerous filamentous organisms, which turned out to be Nocardia asteroides by culture, were also found. After sulfamethoxazole-trimethoprim therapy, all of the skin lesions rapidly decreased in size, with a marked diminution of the number of cytophagic histiocytes, and cleared up within four months. On reporting a case of cutaneous nocardiosis showing unusual histopathologic findings, we considered that reactive conditions should be included in the differential diagnosis of the cutaneous cytophagocytosis, and that nocardiosis could be one of the diseases showing reactive cytophagocytosis.

Molecular and biochemical analysis of AST-1, a class A beta-lactamase from Nocardia asteroides sensu stricto.

A beta-lactamase gene was cloned from a Nocardia asteroides sensu stricto clinical isolate. A recombinant plasmid, pAST-1, expressed the beta-lactamase AST-1 in Escherichia coli JM109. Its pI was 4.8, and its relative molecular mass was 31 kDa. E. coli JM109(pAST-1) was resistant to penicillins and narrow-spectrum cephalosporins. The beta-lactamase AST-1 had a restricted hydrolytic activity spectrum. Its activity was partially inhibited by clavulanic acid but not by sulbactam and tazobactam. AST-1 is an Ambler class A beta-lactamase sharing 65% amino acid identity with beta-lactamase FAR-1, the most closely related enzyme.

[Thoracic nocardiasis associated with macrophage activation syndrome]. / Nocardiose thoracique associée à un syndrome d'activation macrophagique.

Nocardiasis is an uncommon bacterial disease often observed in immunodepressed patients. Its interactions with the immune system remain poorly known. We report a case of Nocardia asteroides thoracic nocaridiasis in an African subject who also had macrophage activation syndrome. We recall the classic data on nocardiasis in Africa and emphasize the importance of emergence in HIV-infected subjects. The association between nocardiasis and macrophage activation syndrome suggest a possible pathogenic mechanism involving the immune system (lymphocytes and macrophages) and Nocardia asteroides.

Antimicrobial susceptibility profile of soil isolates of Nocardia asteroides from Kuwait.

OBJECTIVES: To find the antimicrobial susceptibility profile of 42 soil isolates of Nocardia asteroides against 14 antimicrobial agents representing beta-lactams, aminoglycosides, ciprofloxacin, minocycline, erythromycin and third generation cephalosporins. METHODS: The antimicrobial susceptibility was determined by the disk diffusion method using Mueller-Hinton agar medium. A homogeneous suspension giving an inoculum of 106-108 CFU/mL was used to streak the plates. The zone of inhibition was read after 36-48 h of incubation at 37 degrees C. RESULTS: All the soil isolates of N. asteroides were susceptible to amikacin, imipenem and tobramycin. Susceptibility to cephalosporins was quite variable; 86% of the isolates were susceptible to cefotaxime, 57% to ceftriaxone and 40% to cefamandole. Fifty-seven per cent of the isolates showed intermediate susceptibility to cefamandole, 33% to ceftriaxone and 5% to cefotaxime. Ninety-three per cent of the isolates were resistant to sulfamethoxazole alone or in combination with trimethoprim. CONCLUSIONS: The study reports a wide variation in the antimicrobial susceptibility profile of soil isolates of N. asteroides originating from a single geographical area. Of interest is the finding that over 90% of N. asteroides isolates were resistant to sulfamethoxazole without any previous exposure to this drug. This may have serious therapeutic implications as sulphonamides or the combination of trimethoprim-sulfamethoxazole is the therapy of choice for nocardiosis. Demonstration of resistance to beta-lactam antibiotics may be attributed to the presence of beta-lactamases which was detectable in > 90% of the soil strains of N. asteroides. The study underscores the importance of antimicrobial susceptibility testing for clinical isolates of Nocardia since individual strains show considerable differences in their susceptibility patterns necessitating therapeutic adjustments.

Clinicomicrobiological review of Nocardia keratitis.

PURPOSE: To present the clinical profile, laboratory results, and outcome of treatment in 16 patients with Nocardia keratitis. METHODS: A retrospective review of 16 culture-proven cases of Nocardia keratitis was done. Clinical and microbiologic data were analyzed. RESULTS: Nocardia constituted 1.7% of laboratory-confirmed bacterial keratitis and was seen predominantly in male subjects (13 of 16) with a mean age of 39.1 years. Although the predisposing factor was unknown in the majority, a definite history of trauma was present in four (25%) cases. Patchy stromal infiltrates were seen in 12 patients. Wreath pattern of infiltrates (six of 16) and hypopyon (nine of 16) were notable features. Nocardia was detectable in corneal scrapings of 10 patients with Gram stain and all patients with 1% acid-fast preparation (six of six). Nocardia asteroides was the causative agent in all except one (N. caviae). All isolates were sensitive to gentamicin; however, topical 30% sulfacetamide was the preferred drug for treatment. Favorable outcome (healed scar) was achieved in 11. CONCLUSION: Although Nocardia keratitis is a rare condition, a high index of clinical suspicion should be kept in agricultural workers or in patients with trauma who have patchy stromal infiltrates. Sulfonamides are the initial drug of choice, and gentamicin could be an effective alternative. If recognized early, Nocardia keratitis responds to medical treatment with good visual recovery.

Non-inducible, mainly cell-associated beta-lactamase from Nocardia asteroides strain 108.

The beta-lactamase of the soil-borne strain 108 (parental strain) of Nocardia asteroides is a non-inducible enzyme mainly associated with the cells; it can be efficiently extracted by ultrasonication and SDS treatment. Crude enzyme preparations showed penicillinase and cephalosporinase activity. The kinetics of beta-lactamase production and in-vitro susceptibility to combinations of beta-lactam antibiotics plus beta-lactamase inhibitors have been studied in two stable overproducer mutants (A14 and B1) obtained by mutagenization of the parental strain with nitrosoguanidine. The cell-associated enzyme increased with bacterial growth in parental and mutant strains and was particularly abundant in stationary phase cells. The beta-lactamase inhibitors sulbactam and clavulanic acid decreased MIC values of penicillins more efficiently in the parental strain than in mutants, thus indicating some involvement of the enzyme in the resistance of N. asteroides strain 108 to beta-lactam antibiotics.

Comparison of agar dilution, broth microdilution, disk diffusion, E-test, and BACTEC radiometric methods for antimicrobial susceptibility testing of clinical isolates of the Nocardia asteroides complex.

An evaluation was undertaken to determine the optimal method for the in vitro susceptibility testing of 26 Nocardia asteroides complex isolates to the following antimicrobial agents: amikacin, ampicillin, amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, erythromycin, imipenem, minocycline, and trimethoprim-sulfamethoxazole. Five testing methods were studied including the agar dilution, broth microdilution, and disk diffusion methods, the epsilometer test (E-test), and the BACTEC radiometric method. Results for each antimicrobial agent and each testing method were interpreted as indicating susceptibility, intermediate susceptibility, or resistance according to current guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) for bacteria that grow aerobically and were then compared to a "gold standard" susceptibility test result. The gold standard result for each Nocardia isolate was established by a consensus of the results of the majority of testing methods used in the study. When the results were combined for all antimicrobial agents tested against all Nocardia isolates by all methods, the BACTEC radiometric method produced the highest level of agreement (97.9%) with the consensus results and had the fewest very major (n = 1), major (n = 2), and minor (n = 2) errors. In contrast, the results of the agar dilution method were in least agreement (93.2%) with the consensus results, and this method also produced the most very major (n = 8), major (n = 4), and, along with the disk diffusion method, minor (n = 6) errors. For all test methods, interpretive errors were most frequent when testing ampicillin or amoxicillin-clavulanate. Moreover, for all Nocardia nova isolates tested, ampicillin susceptibility results by any of the testing methods were not in agreement with the results of testing for beta-lactamase by the nitrocefin (Cefinase) disk method. We conclude that among the methods evaluated, the BACTEC radiometric method appeared to be the best for determining the in vitro susceptibilities of members of the N. asteroides complex to a panel of nine antimicrobial agents. However, none of the test methods, including the BACTEC method, accurately predicted the ampicillin resistance of the N. nova isolates tested, all of which produced beta-lactamase. Presuming that this beta-lactamase hydrolyzes ampicillin, this disparity may relate to the NCCLS breakpoints that were used, which may require modification for this antimicrobial agent when tested against N. nova isolates.