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Researchers Identify Risk Factors for Nocardia infection After Solid-Organ Transplant: Presented at ECCMID-ICC

By Chris Berrie

MUNICH, GERMANY -- April 3, 2007 -- High-dose prednisone dosing and cytomegalovirus (CMV) infection in the 6 months, and elevated calcineurin inhibitor level in the preceding 30 days, are independent risk factors for Nocardia infection in patients who undergo solid-organ transplantation.

Principal investigator Anton Y. Peleg, MD, research scholar, Beth Israel Deaconess Medical Centre and Harvard Medical School, Boston, Massachusetts, United States, presented this finding, from a retrospective, matched case-control study here at the joint 17^th European Congress of Clinical Microbiology and Infectious Diseases and 25^th International Congress on Chemotherapy (ECCMID-ICC).

The study also found that empirical combination therapy is recommended for treatment of Nocardia infection in these patients, Dr. Peleg said in a presentation on April 1^st.

The Nocardiae are ubiquitous environmental organisms that belong to a diverse group of aerobic actinomycetes bacteria. The frequency of Nocardia infection is generally at 0.7% to 3.0%, and the majority of infections are seen in recipients of kidney, heart and liver transplants.

"We thought that it was important to look for risk factors to see what we could modify to try and prevent this important infection," Dr. Peleg said. The aim of the study was also to describe the clinical, radiological and microbiological characteristics of Nocardia infection in a large cohort of organ transplant recipients.

The 1:2 matched case-control study enrolled patients with culture proven Nocardia infection treated at the University of Pittsburgh Medical Centre from January 1995 to December 2005. These patients were each matched to 2 controls for transplant type and time of transplantation, using the transplant recipients immediately before and after who survived at least as long as the time to diagnosis of Nocardia in each index case.

Nocardiae infection was identified according to standard procedures and susceptibility testing was carried out in a reference laboratory.

In all, the researchers identified 35 transplant recipients with Nocardia infection (median age, 53 years; male, 66%) out of 5,126 transplantations, giving a frequency for the study centre of 0.68%. This infection rate varied according to transplant type (3.46% lung; 2.55% heart; 0.11% liver; 0.18% kidney; 1.29% small bowel or multivisceral transplants).

No Nocardia infections occurred in pancreas, simultaneous kidney/ pancreas, and heart/ lung recipients.

For 62.9% of cases, the infection was diagnosed within 1 year of transplantation, although 14.3% were diagnosed >5 years from transplantation.

After matching cases with the 70 controls, univariate analysis showed a range of significant risk factors, with multivariable conditional logistic regression analysis revealing 3 independent risk factors. High-dose prednisone therapy in preceding 6 months had an odds ratio (OR) of 27 (95% confidence interval [CI], 3.2-235; P = .003), elevated median calcineurin inhibitor level (i.e. cyclosporine A, tacrolimus) in preceding 30 days OR was 5.8 (95% CI, 1.5-22; P = .012) and CMV disease OR was 6.9 (95% CI, 1.02-46; P = .047).

The researchers identified 4 species of Nocardia -- N. nova (n = 17); N. farcinica (n = 8); N. asteroids (n = 8); N. brasiliensis (n = 1).

All cases received empiric combination therapy, mainly consisting of ceftriaxone IV and trimethoprim-sulfamethoxazole PO or IV (n = 28). Six patients received these therapies alone and 15 in combination with imipenem. With 29 cases receiving definitive therapy after the susceptibility results, trimethoprim-sulfamethoxazole PO was used in 22 patients, either alone (n = 15) or in combination with minocycline (n = 4), amoxicillin/clavulanate (n = 2) or linezolid (n = 1), with a median treatment duration of 6 months.

Nine cases developed a drug-related adverse event that required treatment modification.

A cure was achieved in 89% of Nocardia cases, including 6 of 7 with disseminated disease. However, in comparison with their matched controls, transplant recipients with Nocardia infection had significantly greater 6-month mortality (14.3% vs 1.4%; P = .015).

"There is the need to really be aware of Nocardia infections, specifically in patients who have had their immunosuppression augmented or have had recent CMV disease," Dr. Peleg said.

Similarly, the study suggests the need for combination empiric therapy due to the diversity of the Nocardia species and their variable susceptibilities, the prolonged period before these susceptibilities are known, and the severity of the illness, he said.

Further, use of low-dose trimethoprim-sulfamethoxazole for PCP prophylaxis is in fact unreliable in preventing Nocardia infection in organ transplant recipients, despite its favourable susceptibility results. "So, do not assume that just because your patient is on [low-dose trimethoprim-sulfamethoxazole] prophylaxis, that they cannot get Nocardia infection," he added.

The study in press in the journal Clinical Infectious Diseases.


[Presentation title: Risk Factors, Clinical Characteristics and Outcome of Nocardia Infection in Organ Transplant Recipients: A Matched Case-Control Study Over an 11-Year Period. Abstract P712]

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