Failure of trimethoprim/sulfamethoxazole in invasive Nocardia asteroides infection.

A case of pulmonary nocardiosis occurred with progressive involvement of the pleura, pericardium, mediastinum, and sternum. Surgical resection and drainage procedures followed by administration of the drug combination, trimethoprim/sulfamethoxazole, over a six-month period led to clinical recovery. Discontinuation of drug therapy, however, was followed by relapse and further invasion by the same organism. A literature survey of Nocardia asteroides infections treated with trimethoprim/sulfamethoxazole disclosed that posttreatment follow-up is often too brief or unknown, making the ultimate success of therapy uncertain.     

Nocardia farcinica pericarditis after kidney transplantation despite prophylaxis

Abstract: A deceased-donor kidney transplant recipient developed purulent pericarditis caused by Nocardia despite trimethoprim–sulfamethoxazole (TMP–SMX) prophylaxis for Pneumocystis jirovecii . She was treated empirically with ceftriaxone and amikacin and subsequently underwent sternotomy with drainage of an intrapericardial abscess. Culture and susceptibility data demonstrated Nocardia farcinica , which was susceptible to SMX and amikacin, although resistant to ceftriaxone. Nocardia asteroides , the more common human pathogen, is generally susceptible to third-generation cephalosporins and TMP–SMX. N. farcinica is rare in the United States, more virulent and resistant than N. asteroides , and is more likely to cause disseminated disease. Successful therapy of disseminated Nocardia infections is dependent upon choice of appropriate empiric antibiotics in addition to surgical drainage of purulent fluid collections. TMP–SMX prophylaxis may not be sufficient to prevent infections due to Nocardia species in all immunosuppressed transplant recipients. Here, a rare complication of this unusual pathogen is discussed.     

Disseminated Nocardia otitidiscaviarum in a patient with AIDS

A case of disseminated infection due to Nocardia otitidiscaviarum is described in a Caucasian man infected with the human immunodeficiency virus. The patient presented with no previous AIDS-defining conditions, a CD4 lymphocyte count of 206 cells/mm(3) and enlarging intra-abdominal and chest wall abscesses with bilateral pulmonary infiltrates. Aggressive surgical debridement and antimicrobial therapy with trimethoprim/sulfamethoxazole and amikacin resulted in clinical cure. Long term suppressive therapy was needed to prevent relapse.     

Recurrent Nocardia pneumonia in an adult with chronic granulomatous disease

The diagnosis of chronic granulomatous disease was made for the first time in a young adult when he presented with Nocardia asteroides pneumonia. Treatment with trimethoprim/sulfamethoxazole for 10 wk brought about an apparent cure of the infection. Two and one half years later N. asteroides pneumonia recurred and resulted in death from respiratory failure. Antibiotic susceptibility studies suggested that both episodes were caused by the same organism. This suggestion was supported by endonuclease restriction analysis, which showed that the plasmids from both Nocardia isolates were identical. Late recurrence of pneumonia caused by N. asteroides occurs only rarely. In this patient, recurrent infection appeared to be related to persistence of colonizing organisms in the host.     

Synergistic action of trimethoprim and sulfamethoxazole for Nocardia asteroides: efficacious therapy in five patients

Eighteen isolates of Nocardia asteroides were tested for in vitro susceptibility to trimethoprim (TMP) and sulfamethoxazole (SMZ) alone and in various combinations using disc and paper strip diffusion tests. TMP-SMZ showed synergistic action for two-thirds of teh nocardia isolates tested. Five patients with Nocardia pneumonia were treated with TMP-SMZ and all were cured. Four of the patients' isolates were tested and all showed synergistic patterns of inhibition with the spaced disc and paper strip methods. The agar diffusion disc and synergy tests of TMP-SMZ appear to correlate with clinical usefulness when the Nocardia are susceptible with large zones of inhibition around the combination TMP-SMZ disc.     

Lung infection caused by Nocardia asteroides in a renal-transplant patient

A 65-yr-old man developed an acute lung infection while being treated for a rejection episode 2 months after renal transplantation. A chest X-ray revealed a pulmonary infiltrate. Nocardia asteroides was cultured from a percutaneous lung aspirate. The patient was successfully treated with trimethoprim/sulfamethoxazole.     

Disseminated nocardiosis after unrelated bone marrow transplantation

Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell‐mediated immunity. Although disseminated nocardiosis after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a rare complication, it is associated with high mortality. Moreover, after allo‐HSCT, nocardiosis may be mistaken for other bacterial or fungal infections because clinical and radiographic findings of pulmonary, cerebral, and cutaneous nocardiosis lesions are non‐specific. Here, we report a case of disseminated nocardiosis (caused by Nocardia abscessus) with skin, pulmonary, liver, lymph node, and multiple brain abscesses in a patient after allo‐HSCT. The patient initially responded clinically and radiographically to imipenem/cilastin and trimethoprim‐sulfamethoxazole therapy. Clinicians should be aware of the possibility of nocardiosis in allo‐HSCT recipients who are treated with multiple immunosuppressive agents to control chronic graft‐versus‐host disease. Accurate diagnosis and identification of disseminated nocardiosis is important to ensure administration of the correct antibiotic regimen.     

Molecular diagnosis of fatal Nocardia farcinica pneumonia in an HIV-negative patient

Nocardiosis is a rare and potentially life-threatening infection caused by several species of the Nocardia genus. Most cases occur in immunocompromised patients, and a delay in establishing the diagnosis is common due to the non-specific clinical presentations and the difficulty in cultivating Nocardia. Although the majority of pulmonary nocardiosis cases are caused by Nocardia asteroides, cases of human infection due to N. farcinica are increasingly diagnosed due to recent developments in taxonomy and diagnostic methods. N. farcinica is a separate species from N. asteroides and appears to be more virulent and resistant to antibiotics. Herein, we describe the case of a 65-year-old HIV-negative immunocompromised patient with a fulminant bilateral pulmonary nocardiosis while on empirical treatment with trimethoprim/sulfamethoxazole and imipenem. Post-mortem diagnosis of N. farcinica infection was performed by means of DNA amplification and sequencing of the 65-kDa bacterial heat shock protein.     

Failure of sulfonamides and trimethoprim in the treatment of nocardiosis

An immunocompromised patient with Nocardia brasiliensis pneumonia and empyema acquired disseminated disease due to Nocardia asteroides and died. The treatment of choice for pulmonary or disseminated nocardiosis is 6 to 12 g/day of sulfisoxazole (or adjusted dosage to achieve a serum level of 100 to 150 mg/L) continued for six to 18 months. Combination therapy may be beneficial in selected patients; if trimethoprim therapy is used with sulfonamides, higher than usual doses of trimethoprim may be required to achieve optimal antinocardial activity. When the condition of a patient with nocardiosis falls to improve on sulfonamide therapy, patient compliance should be questioned, serum sulfonamide levels should be measured, cultures and susceptibility studies should be repeated, and a search for sequestered pus should be made.     

Disseminated Nocardia caviae with positive blood cultures.

Disseminated Nocardia caviae infection with multiple positive blood cultures occurred in a bone marrow transplant recipient. Positive blood cultures are unusual in disseminated Nocardia infections and N caviea is an unusual species of Nocardia to cause infections in man, although its virulence in laboratory animals is similar to N asteroides. Multiple positive blood cultures in this case suggest a continuous or recurrent bacteremia rather than a transient bacteremia as previously has been thought to occur in disseminated Nocardia infections. The marked immunosuppressed state of the patient and an indwelling venous line could also have accounted for the recurrent bacteremia.     

Trimethoprim/sulfamethoxazole prophylaxis in neutropenic patients: Reduction of infections and effect on bacterial and fungal flora

A prospective, randomized study was undertaken in neutropenic patients to evaluate the efficacy of prophylactic trimethoprim/sulfamethoxazole in reducing infections and to assess the effect of prophylaxis on bacterial and fungal flora. Fifty-five patients with leukemia, lymphoma, or solid tumors randomly received either one single-strength trimethoprim/sulfamethoxazole tablet twice daily or no drug for the period of expected neutropenia. Trimethoprim/ sulfamethoxazole prophylaxis did not significantly reduce the mean number of febrile days per patient, but did decrease the number of documented infections. The control group experienced 28 infections, including 11 bacteremias and seven infection-associated deaths; the group that received trimethoprim/sulfamethoxazole had seven infections, including two bacteremias and no infection-related deaths. Patients treated with trimethoprim/sulfamethoxazole had no enteric gram-negative bacillary infections compared with 12 infections in the control group. Fungal infections occurred in four control patients but only in one patient who received trimethoprim/sulfamethoxazole. Surveillance cultures revealed that trimethoprim/sulfamethoxazole prophylaxis did not lead to colonization with trimethoprim/sulfamethoxazole-resistant Enterobacteriaceae, Pseudomonas, or fungi. Colonization with filamentous fungi was common in both groups and was related to season of the year rather than prophylactic antibiotic therapy. In conclusion, trimethoprim/ sulfamethoxazole prophylaxis reduced infectious episodes in neutropenic patients without increasing the risk of fungal and trimethoprim/sulfamethoxazole-resistant gram-negative bacillary infections.     

Pulmonary nocardiosis associated with nephrotic syndrome]

A 70-year-old man treated for 6 months with prednisolone for nephrotic syndrome, was referred to our pulmonary division because of a nodule in the right lower lung field. Nocardia asteroides was isolated from the culture of the percutaneous lung aspiration, and the case was diagnosed as pulmonary nocardiosis. The lesion disappeared after 2 months of therapy with sulfamethoxazole/trimethoprim (1,600 mg/320 mg once a day). Though it had been given prophylactically (800 mg/160 mg twice a week) for the prevention of pneumocystis carinii pneumonitis.     

Successful treatment of brain abscess caused byNocardia in an immunocompromised patient after failure of co-trimoxazole

Summary Disseminated infection caused byNocardia asteroides is a fairly rare entity occurring mostly in immunocompromised states. Metastatic brain abscesses are a frequent and ominous complication. We report on a patient whose underlying disease was stage II pulmonary sarcoidosis. He acquired disseminatedN. asteroides infection while on immunosuppressive therapy with prednisolone. After the generally recommended therapy with co-trimoxazole (trimethoprim/sulfamethoxazole) proved ineffective in controlling his brain abscesses, the lesions of the central nervous system completely resolved under a combination of oral rifampicin with i.v. imipenem, followed by oral rifampicin and ampicillin/clavulanic acid.

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Erfolgreiche Chemotherapie eines metastatischen Hirnabszesses mit Nocardia asteroides bei einem immunkompromittierten Patienten nach Therapieversagen von Trimethoprim/Sulfamethoxazol

Zusammenfassung Die disseminierte Infektion mitNocardia asteroides stellt eine äußerst seltene Krankheitsentität dar, welche meistens bei immunkompromittierten Patienten beobachtet wird. Metastatische Hirnabszesse sind eine häufige Komplikation. Wir berichten über einen Patienten mit einer pulmonalen Sarkoidose im Stadium II. Während einer immunsuppressiven Therapie mit Prednisolon erwarb er eine disseminierte Infektion mitN. asteroides. Nachdem die empfohlene Standardtherapie mit Cotrimoxazol ineffektiv in der Kontrolle der erworbenen Hirnabszesse war, heilten diese unter einer kombinierten Therapie mit oralem Rifampicin und Imipenem intravenös, gefolgt von oral verabreichtem Rifampicin kombiniert mit Amoxicillin/Clavulansäure vollständig aus.

     

Double-blind randomized study of prophylactic trimethoprim/sulfamethoxazole in granulocytopenic patients with hematologic malignancies

In a double blind study, oral prophylactic trimethoprim/sulfamethoxazole was evaluated for its utility in preventing serious infections in patients with hematologic malignancy. Of 58 evaluated granulocytopenic episodes in 47 patients, acute leukemia was the underlying malignancy in 46 episodes. Trimethoprim/sulfamethoxazole prophylaxis resulted in fewer microbiologically documented infections (seven versus 15; p = 0.029). This was primarily the result of a reduction in episodes of bacteremia in the trimethoprim/sulfamethoxazole-treated group as compared with the placebo-treated group (three versus nine episodes; p = 0.05). The combined frequency of disseminated candidiasis, candidemia, and esophagitis of presumed fungal etiology was greater in the trimethoprim/sulfamethoxazole-treated group (six) than in the placebo-treated group (two) but not significantly so (p = 0.13). Similarly, there were no significant differences between groups in the overall incidence of infectious complications, number of febrile days, use of parenteral antibiotics, or number of days following randomization to first infectious episode. Throat and rectal surveillance cultures more frequently revealed trimethoprim/sulfamethoxazole-resistant gramnegative bacilli and yeasts in the trimethoprim/sulfamethoxazole-treated group. More frequent emergence of yeast isolates from previously culture-negative patients was documented (p = 0.033). Thus, in this study, trimethoprim/sulfamethoxazole prophylaxis during granulocytopenia reduced the incidence of microbiologically documented infections. However, the emergence of resistant bacteria and of fungi may limit the potential usefulness of this approach.     

Disseminated nocardiosis due to Nocardia otitidiscaviarum:A case report and literature review

Rationale: Disseminated nocardiosis due to Nocardia otitidiscaviarum is rarely reported in immunocompetent hosts.Patient concerns: A 59 year old male patient complained of painful soft tissue swellings and fever for two days.Diagnosis: Disseminated nocardiosis due to Nocardia otitidiscaviarum. Interventions: Initial antimicrobial therapy with imipenem and trimethoprim/sulfamethoxazole was switched to 6 weeks of trimethoprim/sulfamethoxazole, linezolid and tigecycline after sensitivity test results were available. Thereafter, the patient was switched to maintenance trimethoprim/sulfamethoxazole and moxifloxacin. Prednisolone was gradually tapered.Outcomes: Soft tissue swelling and pain disappeared and the patient was discharged uneventfully.Lessons: Disseminated nocardiosis due to Nocardia otitidiscaviarum should be suspected in immunocompetent hosts with risk factors such as medication with prednisolone. Early identification of the causative species and susceptibility results is crucial given the diverse resistance patterns amongst various Nocardia species.     

Nocardial infection as a complication of HIV in South Africa

OBJECTIVES: To assess the occurrence, clinical and microbiological features of nocardial infections complicating HIV in Soweto, South Africa. METHODS: A prospective study was carried out over a 2-year period. Patients were identified after isolation of Nocardia spp. from a clinical specimen. Clinical details were recorded. The nocardial isolates were identified to species level and susceptibility tests performed. RESULTS: Ten patients were identified as having nocardial disease complicating HIV. Clinical presentations were pulmonary (five patients), pulmonary and cerebral (one patient), cerebral (one patient) and skin and soft tissue infection of the lower limb (three patients). Three infections were fatal. The isolates were Nocardia asteroides (seven patients), N. farcinica (two patients) and Nocardia spp. (one). Isolates of N. farcinica demonstrated opacification of Middlebrook agar. All isolates were sensitive to amikacin and minocycline. Most nocardial isolates were susceptible to cefotaxime, imipenem and coamoxiclav. In vitro resistance to cotrimoxazole was present in five. CONCLUSIONS: Nocardial infection occurs as a complication of HIV infection in the Republic of South Africa. Pulmonary cases may be difficult to distinguish from tuberculosis. Nocardia asteroides is the most common species isolated. Nocardia farcinica has resistance to multiple antibacterial agents and demonstrates opacification of Middlebrook agar, a useful screening test for this species. Agents with good in vitro antinocardial activity were amikacin, minocycline, cefotaxime, imipenem and coamoxiclav. There was a high level of resistance in vitro to cotrimoxazole.     

Two cases of Nocardia asteroides sternotomy infection treated with ofloxacin and a review of other active antimicrobial agents.

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.     

Intravenous sulfamethoxazole and trimethoprim for serious gram-negative bacillary infection

Intravenous therapy with sulfamethoxazole and trimethoprim cured seven patients with serious gram-negative infection. Three patients had bacteremia, three had pneumonia, and one each had meningitis, peritonitis, pyogenic liver abscesses, and urinary tract infection. Sulfamethoxazole and trimethoprim was selected in three patients with renal failure to avoid aminoglycoside-induced nephrotoxicity, in three patients because of penicillin allergy, and in two cases because of bacterial resistance to other readily available antibiotics. Adverse drug reactions occurred in three cases and included oral monilia, transient leukopenia, and fluid overload. In contrast to the new broad-spectrum cephalosporin antibiotics, sulfamethoxazole and trimethoprim costs two to 2 1/2 times less and has not been associated with the emergence of bacterial resistance during therapy. This may favor the use of parenteral sulfamethoxazole and trimethoprim for some patients with serious gram-negative infection.     

Treatment of experimental nocardiosis in mice: comparison of amikacin and sulfonamide.

Recent in vitro susceptibility studies have shown that amikacin inhibits more than 90% of isolates of Nocardia. This study was designed to evaluate the effect of treatment with amikacin or sulfonamides on infection caused by Nocardia asteroides with the use of murine models. In an acute lethality model in which infection was induced by intraperitoneal injection, 13 (45%) of 29 mice that had been treated with amikacin survived, in comparison to zero of 39 untreated animals in the control group and one of 39 mice that had been treated with sulfadiazine (P less than 0.001 for amikacin). When infected with a strain of N. asteroides that was resistant to amikacin, all mice that were treated with amikacin and all untreated mice died. Drug therapy was also evaluated in a chronic infection model, in which abscesses were produced by an intraperitoneal injection of N. asteroides in saline. Treatment with either amikacin (P less than 0.001) or sulfonamide (P less than 0.02) for two to three weeks significantly increased the rate of resolution of these abscesses. These murine models demonstrate that amikacin has in vivo activity against Nocardia and may be potentially useful in the treatment of human disease.     

MOLECULAR IDENTIFICATION AND ANTIMICROBIAL RESISTANCE PATTERN OF SEVEN CLINICAL ISOLATES OF Nocardia spp. IN BRAZIL

Nocardia is a ubiquitous microorganism related to pyogranulomatous infection, which is difficult to treat in humans and animals. The occurrence of the disease is on the rise in many countries due to an increase in immunosuppressive diseases and treatments. This report of cases from Brazil presents the genotypic characterization and the antimicrobial susceptibility pattern using the disk-diffusion method and inhibitory minimal concentration with E-test® strips. In summary, this report focuses on infections in young adult men, of which three cases were cutaneous, two pulmonary, one neurological and one systemic. The pulmonary, neurological and systemic cases were attributed to immunosuppressive diseases or treatments. Sequencing analysis of the 16S rRNA segments (1491 bp) identified four isolates of Nocardia farcinica, two isolates of Nocardia nova and one isolate of Nocardia asiatica. N. farcinica was involved in two cutaneous, one systemic and other pulmonary cases; N. nova was involved in one neurological and one pulmonary case; and Nocardia asiatica in one cutaneous case. The disk-diffusion antimicrobial susceptibility test showed that the most effective antimicrobials were amikacin (100%), amoxicillin/clavulanate (100%), cephalexin (100%) and ceftiofur (100%), while isolates had presented most resistance to gentamicin (43%), sulfamethoxazole/trimethoprim (43%) and ampicillin (29%). However, on the inhibitory minimal concentration test (MIC test), only one of the four isolates of Nocardia farcinica was resistant to sulfamethoxazole/trimethoprim.