International Notes Cutaneous Nocardiosis in Cancer Patients Receiving Immunotherapy Injections--Bahamas

From March 1982 to March 1984, 16 persons attending a private cancer immunotherapy clinic in Freeport, Grand Bahama Island, Bahamas, developed abscesses at injection sites after being treated with subcutaneous injections of human serum proteins. The protein injections are prepared by the clinic and then self-administered by the patients. No randomized clinical trials have been performed to determine the effectiveness of the injections. The clinic, which opened in 1977, treats approximately 350 new patients annually.

Organisms recovered from abscesses included Nocardia asteroides (seven patients), Staphylococcus aureus (two), Escherichia coli (one), and an unidentified Actinomyces-like organism (one). One culture yielded no growth; four persons were not cultured. One patient with cutaneous nocardiosis also had pneumonia; N. asteroides was isolated from respiratory secretions obtained during bronchoscopic examination.

Information available from clinic records was not sufficient to define incubation periods or clinical courses of abscesses. However, telephone interviews with patients and their physicians in the United States regarding documented Nocardia infections indicated that the incubation period ranged from 3 hours to 48 hours following injection. In general, patients developed abscesses at multiple injection sites, ranging from 2 cm to 20 cm in diameter. Treatment included incision and drainage, along with antimicrobials such as trimethoprim/sulfamethoxazole. In two patients, however, abscesses were refractory to combination medical and surgical treatment.

Eleven of these 16 persons developed abscesses between November 15, 1983, and March 1, 1984; the attack rate for this period based on a survey of patient charts was 4.5 cases per 100 patients treated. The dates of abscess onset were clustered in three periods: November 16-25, 1983; December 20-30, 1983; and February 16-March 1, 1984. These clusters suggested repeated common-source exposures.

The only common exposure identified among all 16 patients was the self-administration of subcutaneous serum protein injections produced by this clinic. The clustering of the 11 cases in late 1983 and early 1984 suggested that either several lots of serum protein were contaminated during final packaging or that, on several separate days, open vials of serum were contaminated when the daily injections were drawn up. Since medication lot number and patient injection records were not available, it was not possible to test either hypothesis. Limited access to medical records precluded a thorough epidemiologic investigation.

Four serum proteins for injection are produced at the clinic. The proteins are prepared from normal human serum and clots from blood specimens taken from the oncology patients undergoing treatment. Serum and clots are processed by high-speed centrifugation, heat treatment, and ether extraction to produce the proteins. The proteins are reportedly filtered twice through an 0.8-micron filter and then a 0.45-micron filter, packaged in a 6-ml flip-top vial, and frozen until used. The daily set of injections for each resident patient is prepared at the clinic laboratory by filling each syringe directly from an open, multi-dose vial. These syringes are then capped with needles and delivered to the patient for self-administration later. Each patient in residence self-administers six to 12 injections daily; injection sites are rotated between arms, thighs, shoulders, abdomen, and buttocks.

One vial of each of the four protein injections was obtained for culture at CDC. None of the vials tested was sterile, although N. asteroides was not recovered from any of them. Two Staphylococcus species, two Bacillus species, one Acinetobacter species, and one Moraxella-like species were recovered from the protein injections.

It was not possible to identify an environmental source of contamination of the protein vials. It was noted, however, that the protein production area was immediately adjacent to several rooms housing large numbers of laboratory mice used for research. Reported by V Allen, MD, Chief Medical Officer, Ministry of Health, Nassau, Bahamas; M Raff, MD, Louisville, Kentucky; C Shumway, MD, Dillsburg, Pennsylvania; K Lin, MD, Waukegan, R Baker, MD, Chicago, Illinois; Respiratory and Special Pathogens Epidemiology Br, Respiratory and Special Pathogens Laboratory Br, Div of Bacterial Diseases, Div of Mycotic Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: N. asteroides is an aerobic, gram-positive bacterium commonly found in soil. In tissue sections or pus, N. asteroides appears as a beaded branching filament that may be partially or completely acid-fast. N. asteroides grows well on Lowenstein-Jensen medium at 30 C to 37 C; however, it will also grow on blood agar and Saboraud agar. Colonies often appear by 3 days, but growth may take up to 1 week. Laboratories may fail to isolate Nocardia from clinical specimens if plates are discarded after 48 hours (1).

Although nocardiosis is usually a pulmonary infection in humans, Nocardia species have been described as a cause of multiple cutaneous abscesses and draining sinus tracts in cattle (2). However, N. asteroides has rarely been reported as a cause of subcutaneous abscess in humans in North America.

Treatment of abscesses caused by N. asteroides should include incision and drainage and use of an antimicrobial agent to which N. asteroides is sensitive, such as trimethoprim/sulfamethoxazole or minocycline (3). Duration of antimicrobial therapy is uncertain.

Patients receiving immunosuppressives in preparation for organ transplantation have been reported to be at higher risk for disseminated Nocardia infections, and it is likely that oncology patients, such as those attending this immunotherapy clinic, are also at higher risk. Although most of the infections in this cluster were due to N. asteroides, other bacteria were isolated, both from the patients and the protein injections. Physicians should be alert to the possibility of infections in patients receiving immunotherapy and should report such episodes to state health departments.

References

1. Gordon MA. Aerobic pathogenic Actinomycetaceae. In: Lennette EH, Balows A, Hausler WJ Jr, Truant JP, eds. Manual of clinical microbiology. 3rd ed. Washington, D.C.: American Society for Microbiology, 1980:180-94.

2. Lerner PL. Nocardia species. In: Mandel GL, Douglas RG, Bennett JE, eds. Principles and practices of infectious diseases. New York: Wiley Medical, 1979:1962-8.

3. Smego RA Jr, Moeller MB, Gallis HA. Trimethoprim-sulfamethoxazole therapy for Nocardia infections. Arch Intern Med 1983;143:711-8.

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