Nocardia asteroides infection complicating neoplastic disease.
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We describe a case of pulmonary nocardiosis in a patient with rheumatoid arthritis (RA) receiving treatment with combined immunosuppressive agents and prednisone. This infection is still considered rare, hard to diagnose, and difficult to treat. To the best of our knowledge, such a case has not been described in a patient with RA.
HISTORY: A 62 year-old male patient developed malaise, unproductive cough and high temperature (39.5 degrees C) during immunosuppressive therapy with methylprednisolon and cyclosporin A six months after kidney transplantation for glomerulonephritis. INVESTIGATIONS: Clinical examination revealed an endophthalmitis and chest X ray a left-sided lobar pulmonic infiltration. Computed tomography and magnetic resonance imaging examination performed because of recurrent petit-mal-convulsions demonstrated multiple intracranial infiltrations. Transoesophageal echocardiography revealed floating vegetations up to 8 mm in diameter predominantly attached to the aortic valve. A total of 39 consecutive blood cultures drawn during several days remained sterile. However, Nocardia asteroides (Biovar A1) was isolated from a small cutaneous tumor excised from the right thigh. TREATMENT AND COURSE: After initiation of a specific antibiotic treatment with imipenem/cilastatin (each 1 g three times daily), and doxycyclin (100 mg twice daily), computed tomography and magnetic resonance imaging showed a reduction in size and number of the intracranial infiltrations. Neurological symptoms were progressive despite maximal anticonvulsant therapy. The patient died 83 days after hospital admission from an epileptic state resistant to therapy. CONCLUSION: Though nocardiosis is still rare, it should early be included in the differential diagnosis of infections in immunocompromised patients to allow timely diagnosis and therapy.
Nocardia asteroides GUH-2 was administered either intranasally or by intravenous inoculation into (i) conventionally grown, (ii) germfree, and (iii) lipopolysaccharide-treated germfree NIH:S mice. The number of bacteria within the lungs, brain, kidneys, adrenals, liver, spleen, and blood was quantitated at 3, 24, 72, and 168 h after infection. Further, the histological changes that occurred in each of these organs after infection were studied. The data demonstrated that germfree mice were significantly more susceptible to the acute phase of infection caused by N. asteroides than the conventionally grown animals. The brains and lungs of these mice were affected most dramatically. Pretreatment of the germfree mice with lipopolysaccharide completely reversed this enhanced susceptibility and rendered the animals more resistant to infection than the conventionally grown mice. These observations establish further the role of macrophage activation and the development of cell-mediated immunity in host resistance to nocardia. In addition, the presence of a resident microflora within the host appears to be important in the development of resistance to systemic nocardial infections.
Two patients who developed post-operative sternotomy infections due to Nocardia asteroides were treated successfully with ofloxacin, in vitro susceptibility of the organisms being used as a guide to dosage. The place of this drug in the treatment of infection due to Nocardia asteroides merits further investigation.
Nocardia infection occurs primarily among patients with deficient cell-mediated immunity. The portal of entry in the majority of patients with Nocardia infection is pulmonary origin. Central venous catheter-associated bacteremia caused by Nocardia species is very rare, and the optimal management for these situations was indeterminate. Most patients were cured after discontinuation of central venous catheter and prolonged antibiotics use. Thereafter, we reported an 18-year-old male who received chemotherapy for his nasal rhabdomyosarcoma had central venous catheter-associated N. asteroids bacteremia. The outcome was satisfying after discontinuation of central venous catheter followed by short-term antibiotics. Conclusively, prolonged antibiotics may not be necessary in catheter-associated Nocardia bacteremia without distant metastatic site after removal of catheter.
Antimicrobial agents played a miraculous role in the treatment of bacterial infections until resistant bacteria became widespread. Besides antimicrobial-resistant bacteria, many factors can influence the cure of infection. Nocardia infection may be a good example which is difficult to cure with antimicrobial agents alone. A 66-year-old man developed soft tissue infection of the right buttock and thigh. He was given prednisolone and azathioprine for pachymeningitis 3 months prior to admission. Despite surgical and antimicrobial treatment (sulfamethoxazole-trimethoprim), the infection spread to the femur and osteomyelitis developed. The case showed that treatment of bacterial infection is not always as successful as was once thought because recent isolates of bacteria are more often resistant to various antimicrobial agents, intracellular parasites are difficult to eliminate even with the active drug in vitro, and infections in some sites such as bone are refractory to treatment especially when the patient is in a compromised state. In conclusion, for the treatment of infections, clinicians need to rely on laboratory tests more than before and have to consider the influence of various host factors.
A 57-year-old man, treated with immunosuppressive drugs for 3 months after a heart transplantation, developed a painful swelling of the left upper leg and fever. Needle biopsy of the lesion obtained pus from which Nocardia farcinica was cultured. Azathioprine treatment was discontinued and the dosage of cyclosporine reduced. Following antibiotic sensitivity tests, imipenem (4 g/d intravenously) and amikacin (1 g/d intravenously) were administered and the abscess split open. Although the fever responded and dissemination of the infection was excluded the response to treatment was not satisfactory. The drug dosages were repeatedly reduced in response to a rise in serum creatinine concentration to 3.4 mg/dl, deafness, double vision and generalized seizures: the local lesion got worse, but further surgical intervention then brought improvement. After 7 weeks of administration of the above antibiotics, treatment was changed to doxycycline (100 mg/d by mouth). 3 months later computed tomography could no longer demonstrate the lesion.
Nocardia farcinica is a rare Nocardia species causing localised and disseminated infections. A case of Nocardia farcinica infection is presented, and 52 cases previously reported in the literature are reviewed. The hosts usually had predisposing conditions (85%), and acquired the infection through the respiratory tract or skin; the infection then often spread to the brain, kidney, joints, bones and eyes. Pulmonary or pleural infections (43%), brain abscesses (30%) and wound infections (15%) which failed to respond to conventional antimicrobial therapy were the more frequent forms of infection. Nocardia farcinica was frequently isolated from pus (100% of samples), bronchial secretions (41%) and biopsy specimens (63%), but isolation from blood and urine, as in the case presented here, is rare. Antibiotic therapy was adequate in 61% of the patients in whom it was specified, the agents most frequently given being trimethoprim-sulfamethoxazole (54%), amikacin combined with imipenem (7%) and amoxicillin-clavulanate (7%). The high mortality (31%) can be attributed to the severe underlying diseases present, difficulties encountered in identifying the pathogen, inappropriate therapy and late initiation of therapy. Although an infrequent pathogen, Nocardia farcinica should be kept in mind as a cause of infection especially in immunosuppressed patients with indolent infections not responding to third-generation cephalosporins.
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BACKGROUND: Alemtuzumab is being increasingly used for the prevention and/or treatment of acute allograft rejection in organ transplant recipients. We assessed the risks of infection in, to our knowledge, the largest cohort and broadest range of organ transplant recipients yet reported to have received alemtuzumab. METHODS: All patients who received alemtuzumab from September 2002 through March 2004, either as induction therapy at the time of transplantation or for the treatment of rejection, were evaluated for the development of an opportunistic infection (OI) until death or for 12 months after receipt of the last dose of alemtuzumab. RESULTS: A total of 547 recipients were included, 65% of whom received alemtuzumab for induction therapy only. Overall, 56 recipients (10%) developed 62 OIs, including cytomegalovirus disease (n = 16), BK virus infection (n=12), posttransplantation lymphoproliferative disease (n=5), human herpesvirus 6 infection (n=1), parvovirus infection (n=1), esophageal candidiasis (n=12), cryptococcosis (n=2), invasive mold infection (n=4), Nocardia infection (n=4), mycobacterial infection (n=3), Balamuthia mandrillaris infection (n=1), and toxoplasmosis (n=1). Patients who received alemtuzumab for induction therapy were significantly less likely to develop an OI, compared with patients who received alemtuzumab for rejection therapy (4.5% vs. 21%; P<.001). Independent predictors of the development of an OI were administration of alemtuzumab for rejection therapy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.8; P<.001), allograft failure (OR, 2.1; 95% CI, 1.1-4.4; P=.04), and receipt of a lung transplant (OR, 3.7; 95% CI, 1.7-8.0; P=.001) or an intestinal transplant (OR, 8.3; 95% CI, 3.5-19.5; P<.001). CONCLUSIONS: Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received alemtuzumab for induction therapy only. Such data have implications for new antimicrobial prophylactic strategies.
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Pulmonary infection due to Nocardia sp. was investigated in 600 patients of various bronchopulmonary disorders by direct microscopy of sputum samples and cultures on appropriate media. Pathogenic Nocardia species were isolated from 25 patients, giving 4.1% incidence of infection. The species of Nocardia represented were N. asteroides (21 isolates), N. otitidis-caviarum and N. brasiliensis (2 isolates each). Paraffin baiting technique proved to be more efficacious than culturing on glucose nutrient agar.
Two cases of nocardiosis, an uncommon disease in HIV patients, are presented. Considerations concerning diagnosis, clinical pictures, treatment and prophylaxis are discussed. Because of profound morbidity and mortality, the possibility of Nocardia infection should be suspected in cases of pulmonary infection where more common pathogens cannot be found.
A case of a healthy girl with a trauma in her right leg is described. Twelve hours later she developed fever and pain in the inguinal region. Two days later, she was admitted to the Hospital, and there, an aspiration of pus from the lymph node was performed, and this sample was sent for culture. The Gram smear showed gram-positive filamentous bacilli and when Kinyoun was used they were observed as weakly acid fast rods. After four days of incubation under aerobic conditions, white and hemolitic colonies were seen on human blood agar plates. Biochemical tests as urea hydrolysis and gelatin liquefaction were performed. To complete the identification it was sent to a reference laboratory, INEI-ANLIS Dr. Carlos G. Malbrán, where the isolate was confirmed as Nocardia asteroides sensu stricto. The patient was treated with intravenous cephalotin with good evolution. Therapy was followed with oral trimethoprim-sulfamethoxazole. This case is the first report of a Nocardia infection in the Hospital de Niños de Santa Fe. The fact that N. asteroides was isolated from an immunologically competent girl should be highlighted. This species is uncommon in children and it is rare in our region. In addition, N. asteroides infections are usually seen in pulmonary disease and rarely producing cutaneous infections.
Disseminated Nocardia infection has a high mortality and morbidity rate in solid organ transplant recipients, even when appropriate antibiotics are given. In this report a renal transplant recipient is described, who developed disseminated Nocardia asteroides infection with lung, eye, and brain involvement, in addition to coinfection with Trichophyton rubrum.
OBJECTIVE: Nocardiosis is a very rare, opportunistic infection caused by microorganisms of the genus Nocardia, and is associated with significant morbidity and mortality in kidney transplant patients receiving immunosuppressive therapy. MATERIAL AND METHODS: Since 1980, our Renal Transplant Unit has carried out 1239 kidney transplants, and five cases of Nocardia infection have occurred during this time. In this retrospective study, special consideration is given to clinical manifestations, treatment response (efficacy and side-effects) and the evolution of both the patient and the graft. Microbiological factors studied included biochemical profiles and antimicrobial sensitivity. RESULTS: Nocardiosis was observed in five men with a mean age of 49.2 years who had received immunosuppressive therapy (generally cyclosporin/azathioprine and prednisone) for a mean of 47.8 months (range 1-148 months). Four of the patients had good previous renal function. The clinical presentation of nocardiosis was as follows: pleuropulmonary pattern of infection, n = 3; subcutaneous abscess, n = 1; and fulminant multi-organ disseminated nocardiosis, n = 1. In all cases, direct observation using modified Ziehl-Neelsen staining proved positive, and in vitro culture revealed good sensitivity to trimethoprim-sulfamethoxazole and variable sensitivity to the other groups of antibiotics. Nocardia brasiliensis was isolated in two cases, and Nocardia asteroides in three. Two patients died, one due to multiple organ involvement and the other due to acute respiratory failure associated with severe hepatopathy caused by hepatitis C virus. The remaining cases improved. CONCLUSION: A low incidence of nocardiosis following kidney transplantation was observed. Fatal cases occurred in patients with bacteremia and serious comorbid medical conditions, in whom early diagnosis and specific treatment was required.