Pseudomonas aeruginosa Infections After Transplant Rare But Deadly

CHICAGO—Fifteen to 20 years ago, treatment of patients infected with Pseudomonas aeruginosa infection after stem cell transplantation was limited to certain beta-lactam and aminoglycoside antibiotics that were active against the organism.

Because newer antibiotics, such as the fluoroquinolones and the cephalosporins cefotaxime (Claforan) and cefepime (Maxipime), have greater activity against P aeruginosa and less toxicity than previously prescribed antibiotics, there has been every reason to believe that treatment has improved and mortality has declined.

According to a study from Fred Hutchinson Cancer Research Center, Seattle, P aeruginosa infections occur only rarely after stem cell transplantation, but overall mortality exceeds 30%. More than 35% of patients relapse after antibiotic treatment, and for these individuals, mortality is 90%.

"Even though the incidence of these infections is only about 1%, when these people get infected, they have a very poor prognosis for the initial infection. Once the initial infection appears to be treated successfully, there is still a fairly high risk of relapse, and when patients do relapse, the prognosis is terrible," said Morgan Hakki, MD, a senior fellow in the Program in Infectious Diseases at Fred Hutchinson.

46 Cases of Invasive P aeruginosa

The study, presented in a poster session at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC abstract 780), was a retrospective review of 46 cases of invasive P aeruginosa infection in individuals who underwent hematopoietic stem cell transplantation between 1990 and 2000.

Although patients were treated with combination antibiotics for an average of 16.8 days, the mortality rate attributable to P aeruginosa was 31.4%. Ten of 28 survivors (35.7%) relapsed with P aeruginosa infection a median of 9 days after the cessation of antibiotic therapy, and 90% of these individuals died within 36 days.

Investigators at Hutchinson then studied infection with other gram-negative organisms to determine if the mortality rates seen with P aeruginosa were unique. "We found that, for the most part, infection with other gram-negative organisms carries a lower mortality rate than infection with P aeruginosa. However, infection with certain organisms, such as Escherichia coli and Enterobacter, had similar mortality rates," Dr. Hakki said.

The researchers also examined factors that might predict which patients would survive P aeruginosa infection and which would not. The most significant factors predicting death were infection with other pathogens (P = .04), neutropenia (P = .02), neutropenia plus infection with another pathogen (P = .006), and neutropenia plus steroid use (P = .04).

Reviewing Treatment Guidelines

The results of these studies have led clinicians at Hutchinson to review antibiotic treatment guidelines for invasive bacterial infections in patients after stem cell transplantation.

As Dr. Hakki explained, "There are no real guidelines for treating infections of this type in this patient population. The standard course of antibiotic treatment for gram-negative infections is listed as 2 to 3 weeks in textbooks. However, there is nothing to say how this particular patient population should be treated."

Consequently, the Hutchinson researchers are considering treating stem cell transplant patients who develop invasive bacterial infections for more than 2 to 3 weeks.

"We have no randomized data to suggest that using treatment longer than the standard course of antibiotics would work, but one option might be to extend treatment with an oral agent that is not too toxic and has activity against P aeruginosa, such as one of the fluoroquinolones, beyond the usual 2 to 3 weeks of initial intravenous therapy," Dr. Hakki commented.

There is a theoretical risk associated with extending therapy with oral fluoroquinolone monotherapy, Dr. Hakki said, which is why this decision must be made after careful review of the underlying processes that may contribute to relapse of infection, such as the original source of the infection as well as the use of steroids or other oral immunosuppressive medications.

The study findings also reaffirmed the influence that host factors exert on mortality following any infection and the need for aggressive management of such factors as neutropenia. "Perhaps neutropenia should be treated with G-CSF (Neupogen) to boost neutrophil counts or possibly even granulocyte transfusions, if they are available," he said.

Infection with any sort of copathogen—viral, fungal, or other bacteria—should be treated as aggressively as possible, he emphasized. "This study confirms that anything you can do to help with host defense most likely will be beneficial."