Treating cancer-related infections: Here's how

June 18, 2007

In an effort to keep pace with advances in the management of infectious complications in immunosuppressed cancer patients who are hospitalized, the National Comprehensive Cancer Network has released updated guidelines for the prevention and treatment of cancer-related infections.

Infection is often a serious complication among immunosuppressed cancer patients who are hospitalized. In an effort to keep pace with advances in the management of infectious complications in these patients, the National Comprehensive Cancer Network (NCCN) has released updated guidelines for the prevention and treatment of cancer-related infections. The new guidelines can be found at http://www.nccn.org/.

The guidelines stress that the cornerstone of infection management for febrile neutropenic patients is prompt initiation of empiric, broad-spectrum antibiotics. Based on evidence from randomized studies, the panel advocates initial monotherapy with either a carbapenem antibiotic, such as imipenem/cilastatin (Primaxin, Merck) or meropenem (Merrem, AstraZeneca), or an antipseudomonal cephalosporin, such as cefepime (Maxipime, Bristol-Myers Squibb) or ceftazidime (Fortaz, GlaxoSmithKline). Stuntebeck pointed out that the updated guidelines have added piperacillin/ tazobactam (Zosyn, Wyeth) as a choice for monotherapy, a decision supported by favorable results from clinical trials. She emphasized that practitioners must know local institutional susceptibility patterns prior to initiating monotherapy.

According to the guidelines, the duration of antibiotic therapy depends mainly on the patient's clinical condition along with response to treatment and recovery of neutrophils, the site of infection, and the causative pathogen. It is usually recommended that antimicrobials be continued until the absolute neutrophil count (ANC) is above 500 cells/mm3, in cases of fever of unknown etiology.

"The updated guidelines have also put more emphasis on the prevention of infections in cancer patients," stated Stuntebeck. The panel has incorporated recommendations for antibacterial, antifungal, and antiviral prophylaxis based on risk groups. For low-risk patients, who are not on immunosuppressants and anticipated to have a short duration of neutropenia, antibacterial prophylaxis is not necessary. Prophylaxis with fluoroquinolones may be considered for intermediate-risk patients, including those with hematologic malignancies or receiving purine analogs, and high-risk patients, such as allogeneic HSCT recipients.

The guidelines also include prophylaxis recommendations for certain high-risk, non-neutropenic patients. Penicillin and trimethoprim/ sulfamethoxazole (TMP/SMX) prophylaxis for patients with graft-versus-host disease (GVHD) and TMP/SMX for patients receiving alemtuzumab is suggested.

To avoid emergence of resistant fungal pathogens, the panel warns, antifungal prophylaxis should not be used routinely in all neutropenic patients. The rationale for antifungal prophylaxis is to prevent fungal infections in a targeted group of high-risk patients, such as those with myelodysplastic syndrome, AML, and allogeneic HSCT recipients with GVHD. Based on recent published data, the panel included posaconazole (Noxafil, Schering) as an option for antifungal prophylaxis for these high-risk patients. Of note, the guidelines advocate fluconazole for prophylaxis in acute lymphocytic leukemia (ALL) patients receiving vinca alkaloids such as vincristine.

Posaconazole and other azole antifungals were not recommended in ALL-based regimens primarily because they are potent inhibitors of cytochrome P450 enzymes and may significantly decrease clearance of vinca alkaloids.