Disseminated Nocardia infection with a lesion occupying the intracranial space complicated with coma: a case report.

BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.

An Unusual Presentation From a Sporadic Partially Acid-Fast Aerobic Actinomycete Resistant to Common Antibiotics.

Nocardia causes rare opportunistic infections, that can be challenging to diagnose because of atypical features on conventional microbiological identification techniques. Immunosuppressed patients are more susceptible to infections from Nocardia and are associated with multi-organ involvement. We report a case of a 63-year-old male who developed peritonitis from Nocardia farcinica that rarely causes infections in humans. The nonspecific symptoms, negative blood cultures, and slow growth can make diagnosis difficult. Despite aggressive therapy, the virulence and inherent resistance to the antibiotics can result in high mortality from Nocardia farcinica infections.

Management of Nocardia Interface Keratitis After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To report the clinical course and management of graft-host interface Nocardia keratitis after Descemet membrane endothelial keratoplasty (DMEK). METHODS: A 70-year-old man presented with a corneal epithelial defect, stromal edema, graft infiltrate, and graft-host interface infection 5 months after an uneventful DMEK performed for bullous keratopathy in the left eye. Corneal scrapings from the margin of epithelial defect showed gram-positive bacillus, and the organism was identified as Nocardia asteroides. RESULTS: Intensive and appropriate topical and systemic antibiotic therapy resulted in complete resolution of infection. Three months later, the patient underwent a repeat DMEK, which resulted in clearing of corneal edema and improvement in visual acuity. CONCLUSIONS: Nocardia interface keratitis is a rare entity, which can occur after DMEK. Proper clinical evaluation and microbiological workup helped us in accurate diagnosis and management. Repeat DMEK after complete resolution of the infection resulted in good outcomes regarding corneal clarity and vision improvement.

Dehydropropylpantothenamide isolated by a co-culture of Nocardia tenerifensis IFM 10554T in the presence of animal cells.

A new amide, named dehydropropylpantothenamide (1), was obtained by a co-culture of Nocardia tenerifensis IFM 10554T in the presence of the mouse macrophage-like cell line J774.1 in modified Czapek-Dox (mCD) medium. Compound 1 was synthesized from D-pantothenic acid calcium salt in 6 steps. The absolute configuration of natural compound 1 was determined by comparisons of the optical rotation and CD spectra of synthetic 1. In the present study, a new method for producing secondary metabolites was demonstrated using a "co-culture" in which the genus Nocardia was cultured in the presence of an animal cell line.

Multidrug-resistant Nocardia pseudobrasiliensis presenting as multiple muscle abscesses.

A 79-year-old Caucasian man presented with multiple leg abscesses due to Nocardia pseudobrasiliensis. He was on chronic steroid therapy for myasthenia gravis. We present the difficulties in diagnosis and treatment of this rare organism. N. pseudobrasiliensis is a new emerging species that was previously thought to belong to the N. brasiliensis species. The distinction between the two species is extremely important given the different antibiotic susceptibility pattern and association of N. pseudobrasiliensis with more invasive and disseminated disease.

The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial.

PURPOSE: To determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes. DESIGN: Randomized, placebo-controlled, double-masked clinical trial. METHODS: This multicenter trial compared 1.0% prednisolone sodium phosphate to placebo in the treatment of bacterial keratitis among 500 patients with culture-positive ulcers receiving 48 hours of moxifloxacin before randomization. The primary endpoint was 3 months from enrollment, and 399 patients were evaluated at 12 months. The outcomes examined were best spectacle-corrected visual acuity (BSCVA) and scar size at 12 months. Based on previous results, regression models with adjustments for baseline status and/or causative organism were used for analysis. RESULTS: No significant differences in clinical outcomes by treatment group were seen with the prespecified regression models (BSCVA: -0.04 logMAR, 95% CI, -0.12 to 0.05, P = .39; scar size: 0.03 mm, 95% CI, -0.12 to 0.18, P = .69). A regression model including a Nocardia-treatment arm interaction found corticosteroid use associated with a mean 1-line improvement in BSCVA at 12 months among patients with non-Nocardia ulcers (-0.10 logMAR, 95% CI, -0.19 to -0.02, P = .02). No significant difference was observed in 12-month BSCVA for Nocardia ulcers (0.18 logMAR, 95% CI, -0.04 to 0.41, P = .16). Corticosteroids were associated with larger mean scar size at 12 months among Nocardia ulcers (0.47 mm, 95% CI, 0.06-0.88, P = .02) and no significant difference was identified by treatment for scar size for non-Nocardia ulcers (-0.06 mm, 95% CI, -0.21 to 0.10, P = .46). CONCLUSIONS: Adjunctive topical corticosteroid therapy may be associated with improved long-term clinical outcomes in bacterial corneal ulcers not caused by Nocardia species.

Fluoroquinolone treatment and susceptibility of isolates from bacterial keratitis.

OBJECTIVE: To analyze the relationship between fluoroquinolone use at presentation and minimum inhibitory concentration in bacterial keratitis. METHODS: The Steroids for Corneal Ulcers Trial was a randomized, double-masked, placebo-controlled trial assessing the effect of adjunctive topical corticosteroid treatment on outcomes in bacterial keratitis. After presentation, all patients were treated with moxifloxacin hydrochloride, 0.5%. We compare antibiotic use at presentation with minimum inhibitory concentration against moxifloxacin for all isolates. Separate analyses accounted for organism species and fluoroquinolone generation. RESULTS: Topical fluoroquinolone use at presentation was reported in 92 of 480 cases (19.2%). Causative organisms in the 480 cases included Streptococcus pneumoniae (247 cases [51.5%]), Pseudomonas aeruginosa (109 cases [22.7%]), and Nocardia species (55 cases [11.5%]). Isolates from patients who reported fluoroquinolone use at presentation had a 2.01-fold-higher minimum inhibitory concentration (95% CI, 1.39-fold to 2.91-fold; P < .001). Fourth-generation fluoroquinolones were associated with a 3.48-fold-higher minimum inhibitory concentration than those isolates that were not exposed to pretreatment at enrollment (95% CI, 1.99-fold to 6.06-fold; P < .001). CONCLUSION: This study provides evidence that prior use of fluoroquinolones is associated with antibiotic resistance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00324168.

Disseminated Nocardiosis caused by Nocardia concava with acute respiratory failure and central nervous system involvement treated with linezolid.

Nocardia concava was identified as a new species in 2005; however, the clinical manifestations of Nocardia concava infection have yet to be clarified. We herein present the case of an immunosuppressed patient who developed disseminated nocardiosis caused by N. concava with multiple abscesses in the lungs, cutis, subcutaneous tissue, skeletal muscles and kidneys accompanied by central nervous system involvement, including meningitis and ventriculitis. The patient was cured with appropriate treatment including linezolid after testing for susceptibility. Linezolid should be considered as an alternative agent for treating disseminated nocardiosis because of its effective distribution to multiple sites.

Nocardia keratitis: clinical course and effect of corticosteroids.

PURPOSE: To compare the clinical course of Nocardia species keratitis with keratitis resulting from other bacterial organisms and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial. DESIGN: Subgroup analysis of a randomized controlled trial. METHODS: setting: Multicenter randomized controlled trial. study population: Five hundred patients with bacterial keratitis randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin. intervention/observation procedure: Topical prednisolone phosphate 1% or placebo and clinical course of Nocardia keratitis. main outcome measures: Best spectacle-corrected visual acuity and infiltrate or scar size at 3 months from enrollment. RESULTS: Of 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared with non-Nocardia ulcers (median Snellen visual acuity, 20/45, compared with 20/145; P < .001) and comparable 3-month visual acuity (median, 20/25, vs 20/40; P = .25). Nocardia ulcers had approximately 2 lines less of improvement in visual acuity compared with non-Nocardia ulcers (0.21 logarithm of the minimal angle of resolution; 95% confidence interval, 0.09 to 0.33 logarithm of the minimal angle of resolution; P = .001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4-mm increase in 3-month infiltrate or scar size (95% confidence interval, 0.03 to 0.77 mm; P = .03). CONCLUSIONS: Nocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes.

Clinical and microbiological characteristics of infections caused by various Nocardia species in Taiwan: a multicenter study from 1998 to 2010.

This multicenter study in Taiwan investigated the clinical presentations of various Nocardia species infections based on 16S rRNA sequence analysis. Patients with nocardiosis in four large medical centers from 1998 to 2010 were included. A total of 100 preserved nonduplicate isolates causing human infection were identified as Nocardia species. Sequencing analysis of 16S rRNA confirmed that 35 of 36 N. asteroides isolates identified by conventional tests were non-asteroides Nocardia species, and that two of 50 N. brasiliensis isolates had also been initially misidentified. N. brasiliensis (50%) was the most common pathogen, followed by N. cyriacigeorgica (18%). In addition, several rare pathogens were identified, including N. asiatica, N. rhamnosiphila, N. abscessus, N. transvalensis, N. elegans, and N. carnea. Primary cutaneous infection was the most common presentation, noted in 55 (55%) patients, while pulmonary infection presented in 26 (26%) patients. The crude mortality rate was 6.7% (6/89), and was lowest for primary cutaneous infection (2.2%) and highest for disseminated disease and pulmonary infection (16.7%). In conclusion, N. brasiliensis and N. cyriacigeorgica were the most common pathogens causing nocardiosis in Taiwan. Molecular methods for identifying Nocardia to the species level are mandatory for better understanding the epidemiology and clinical characteristics of patients with nocardiosis.

In vitro activity of multiple antibiotic combinations against Nocardia: relationship with a short-term treatment strategy in heart transplant recipients with pulmonary nocardiosis.

BACKGROUND/OBJECTIVES: Pulmonary nocardiosis (PN) chiefly affects immunocompromised patients, particularly transplant recipients. Cotrimoxazole is still the mainstay of treatment, but it is associated with nephro- and myelo-toxicity, and can show unpredictable activity against Nocardia isolates. METHODS: Over a 20-year period, Nocardia isolates were identified from 12 heart transplant (HTx) recipients with PN. The in vitro activity of various antibacterials, alone or in combination, was assessed using disk-diffusion, minimal inhibitory concentration (MIC), and time-kill methodology. The in vitro results were compared with the clinical outcome of the patients. RESULTS: Seven different Nocardia strains were identified. Disk diffusion and MIC determinations showed that all isolates were susceptible to amikacin, netilmicin, and linezolid, and that moxifloxacin was the most active of the fluoroquinolones. All but 1 of the isolates were susceptible to imipenem. Time-kill studies showed that imipenem/amikacin and imipenem/moxifloxacin combinations were bactericidal for most isolates. Of 12 patients who received 3-4 weeks' intravenous (IV) treatment with amikacin or ciprofloxacin in combination with a beta-lactam, followed by 1-3 months' oral cotrimoxazole, moxifloxacin, or linezolid, 11 were cured; 1 patient died, but not related to Nocardia. CONCLUSION: Initial PN treatment in HTx recipients can be successfully carried out with bactericidal combinations such as imipenem plus amikacin or moxifloxacin, administered IV for 3-4 weeks. Within 1 month, a significant clinical and radiological improvement may be observed. In our experience, a <3 month oral regimen with cotrimoxazole, moxifloxacin, or doxycycline may then be used. This may allow a reduction of side effects and treatment-related burden, without any recurrence.

Posttraumatic ankle arthritis due to a novel Nocardia species.

INTRODUCTION: Nocardial arthritis in immunocompetent patients is rare, and the optimum duration of antimicrobial therapy is unknown, although several months of antibiotic treatment is often recommended. CASE REPORT: We here report the first case of human infection with a novel Nocardia sp., summarise the epidemiology of nocardial arthritis and outline the feasibility of relatively short antibiotic treatments after careful surgical drainage.

Antimicrobial activity screening of some sulfonamide derivatives on some Nocardia species and isolates.

Nocardia are aerobic, catalase-positive, Gram-positive microorganisms and typically acid-alcohol fast at some stage of the growth cycle. The genus Nocardia, a member of Mycolata group, is clinically important because it is an opportunistic pathogen. The sulfonamide derivative medicines are prefered to cure infection caused by Nocardia, such as nocardiaosis and mycetoma. Antimicrobial activities of seven sulfonamide derivatives have been investigated against some Nocardia species and isolates using the disk diffusion method on Sensitest agar medium (Oxoid). Thirty-six organisms, which consisted of 10 soil isolates selected from different clusters of Aymen study (2003), six clinical isolates provided by Ege University, Medical School, Microbiology and Clinical Microbiology Department, four reference strains, 15 type strains and a control strain of Staphylococcus aureus ATCC 43300 were tested. The strongest inhibition was observed in the cases of IV [N-(2-hydroxy-4-nitro-phenyl)-4-methyl-benzensulfonamid], V [N-(2-hydroxy-5-nitro-phenyl)-4-methyl-benzensulfonamid] and III [N-(2-Hydroxy-phenyl)-4-methyl-benzenesulfonamide] against Nocardia. Introducing a hydroxyl group into the ortho position on the ring increased the antimicrobial activity. Substitution of the electron withdrawing groups such as a nitro group increased the antimicrobial activity remarkably.

[Pulmonary nocardiosis with trimethoprime/sulphamethoxazole-resistant Nocardia paucivorans in a patient with no signs of immunosuppression]. / Pulmonale Nokardiose mit Trimethoprim/Sulfamethoxazol resistenter Nocardia paucivorans bei einem Patienten ohne Hinweise auf Immunsuppression.

This is so far the first published case report of a Nocardia paucivorans infection in an immunocompetent patient. A 54-year-old farmer was hospitalised with a history of coughing and fever for a period of five months. There was no indicator of either primary of secondary immunodeficiency in the prior medical history. A chest X-ray showed pneumonic infiltrates in the right middle und lower lobes, which progressed despite of antibiotic therapy with macrolides. A transbronchial biopsy revealed unspecific granulomatous inflammation of soft tissues. N. paucivorans - grew in cultures of sputum, bronchoalveolar lavage, and transbronchial biopsy. Oral antibiotic therapy was started with trimethoprime-sulphamethoxazole (TMP/SMX) and amoxicillin plus clavulanic acid. Susceptibility testing revealed high level resistance to TMP/SMX, which was consequently replaced by ciprofloxacin. Six months later, infiltrates had completely resolved and the patient did not report any residual clinical symptoms. The present case showed once again that nocardiosis is not limited to patients with immunodeficiencies. However, conservative combination therapy with oral antibiotics seems to be sufficiently effective for nocardiosis in the immunocompetent patient. For cases of suspected nocardiosis, a step-wise, risk-based diagnostic and therapeutic procedure is proposed.

Intracranial Nocardia recurrence during fluorinated quinolones therapy.

Nocardia infection is a well-recognized complication in renal transplant recipients and other immunocompromised hosts. It is mostly a primary pulmonary infection, which can disseminate to other organs in half of the cases. Nocardiosis is a life-threatening infection. Therefore, an efficient long-lasting treatment must be rapidly administered. We report 1 case of disseminated nocardiosis with pulmonary involvement, brain lesions, and bone lesions in a renal transplant patient, who was treated with stereotactic aspiration in association with high dose of trimethoprim/sulfamethoxazole (TMP/SMX) and imipenem, changed, after 3 weeks to moxifloxacin. First, clinical manifestations decreased after surgical drainage and combination therapy with the 2 antimicrobial agents, but later the patient developed a recurrence of brain lesions during treatment with quinolones. Consequently, the patient was again treated with TMP/SMX and imipenem, after which the patient recovered. It is surprising that moxifloxacin was efficient in vitro and the antimicrobial concentration in the central nervous system was high, yet the nocardial abscess recurred under this therapy.

Trimethoprim-sulphamethoxazole therapy in Nocardia keratitis.

PURPOSE: To describe the clinical features, microbiological features and treatment outcome of nine patients with Nocardia keratitis treated with topical trimethoprim- sulphamethoxazole drops. METHODS: Retrospective review of nine patients with culture-proven Nocardia keratitis. RESULTS: Nine patients with Nocardia keratitis were treated with topical trimethoprim-sulphamethoxazole drops. The average duration of treatment was 25 +/- 9 days. Five of the nine patients presented with superficial ulcers with margins studded with yellowish white discrete pinhead sized infiltration; the other four patients had deep stromal infiltration. Complete healing of the ulcer was achieved in six out of the nine patients with topical trimethoprim- sulphamethoxazole alone or in combination with ciprofloxacin 0.3% eye drops. CONCLUSION: Topical application of trimethoprim-sulphamethoxazole appears to be effective therapy for superficial keratitis due to Nocardia.