Thomas L. Kuhls

Rhodococcus equi infections of humans. 12 cases and a review of the literature.

Increased recognition of Rhodococcus equi as a human pathogen has occurred since 1983, when the first review article summarized the worlds literature of 12 cases. In this article, we present 12 cases from the University of Oklahoma Health Sciences Center and review 60 from the literature. Most cases occur in immunocompromised hosts and present as chronic cavitary pneumonias. Associated extrapulmonary disease is seen at diagnosis in 7% of patients with pneumonia, and relapse occurs at extrapulmonary sites in 13%, often without reappearance of pulmonary disease. Relapse may follow a course of antimicrobial therapy that is too brief, but can also occur during treatment. Infections also occur in the gastrointestinal tract, causing enteritis and regional adenitis with abscesses. Contaminated wounds may become infected. Isolated bacteremias may be a manifestation of latent infection recurring during a period of immune suppression. A common feature of human R. equi infection is delay in diagnosis. The insidious course of disease contributes to delay, as does failure to identify the organism. R. equi is easily cultured on nonselective media but commonly mistaken for a diphtheroid or occasionally for a mycobacterium based on acid-fast appearance. Form and duration of treatment are closely related to host immune status. Immunocompromised patients require prolonged or indefinite therapy with multiple antibiotics. Infections in immunocompetent hosts are easily treated with short courses of single agents. Infections related to contaminated wounds are treated primarily by irrigation and debridement. Infections in immunocompromised hosts are increasing in frequency largely due the AIDS epidemic. Infections in immunocompetent hosts, reported rarely before this series, may be underdiagnosed, perhaps because R. equi resembles common commensals and has limited virulence in this population. This report demonstrates that R. equi infections, including community-acquired pneumonias, occur in immunocompetent hosts.

Cryptosporidium parvum infection after abrogation of natural killer cell activity in normal and severe combined immunodeficiency mice.

The role of natural killer (NK) cell activity in adult mice with severe combined immunodeficiency (scid mice) infected with Cryptosporidium parvum oocytes was evaluated. Adult BALB/c and scid mice were inoculated intragastrically with 10(6) C. parvum oocysts after the administration of anti-asialo-GM1 or control normal rabbit serum. Groups of animals were evaluated for splenic NK cell activity and examined histopathologically at 2, 4, and 6 wk postinfection. Virtual elimination of splenic NK cell activity by anti-asialo-GM1 treatment was demonstrated. Nonetheless, no differences in the occurrence of illness, death, or histopathologic evidence of infection were observed between anti-asialo-GM1-treated and control-treated BALB/c or scid mice. We conclude that NK cell activity, at least as measured in the spleen, does not play a significant role in murine host defense of cryptosporidial infection, even in the absence of functional B and T cells.

Inability of Interferon-Gamma and Aminoguanidine to Alter Cryptosporidium parvum Infection in Mice with Severe Combined Immunodeficiency

Severe combined immunodeficiency (scid) mice have been useful in identifying specific host defense systems responsible for containing and eradicating Cryptosporidium parvum infection. Adult scid mice were given C. parvum oocysts and treated weekly with monoclonal antimurine interferon-gamma (anti-IFN-gamma). Anti-IFN-gamma-treated mice had more cryptosporidia seen in the intestines and had more severe morphologic changes associated with disease than control mice. To assess the mechanism of this effect, infected adult BALB/c and scid mice were treated with the nitric oxide synthase inhibitor, aminoguanidine. Infection in aminoguanidine-treated mice was not significantly different from that in control mice. Next, the effects of pharmacologic doses of IFN-gamma (10,000 IU) on the course of cryptosporidiosis in newborn scid mice were evaluated. IFN-gamma did not reverse the initial susceptibility of neonatal scid mice to cryptosporidiosis and continued treatment with IFN-gamma (10,000 IU weekly) did not alter survival. We conclude that IFN-gamma does not exert its anticryptosporidial effect by stimulation of nitric oxide production. Deficient IFN-gamma production by neonatal lymphocytes does not appear to be responsible for the increased severity of infection observed in neonatal animals. Also, IFN-gamma may not be useful in treating immunocompromised patients with cryptosporidiosis.

Use of aminoglycosides during cyclosporine A immunosuppression after liver transplantation in children.

To determine the frequency of renal dysfunction associated with the use of aminoglycosides with cyclosporine A (CyA) in children, the records of 26 consecutive children receiving CyA after liver transplantation were reviewed. Fourteen patients with normal baseline serum creatinine concentrations received an aminoglycoside postoperatively. These children received CyA and an aminoglycoside for 249 days (average, 17.8 days/patient). Forty of the 249 days included treatment with vancomycin or amphotericin B. Twelve children (86%) showed no evidence of renal dysfunction after aminoglycoside therapy. Two children developed renal dysfunction and eventually succumbed. In neither case could aminoglycoside nephrotoxicity be identified as the main cause of renal dysfunction. Multiple other factors, including ischemia and high CyA concentrations, probably contributed to renal deterioration. We conclude that aminoglycosides can be used safely in children receiving CyA following liver transplantation, provided serum CyA concentrations are followed closely and other risk factors for renal dysfunction are minimized.

Bismuth Subsalicylate Prophylaxis of Cryptosporidium parvum Infection in Immunodeficient Mice

I Bismuth subsalicylate (BSS) and other bismuth salts formed after oral administration of BSS have activity in a number of diarrheal diseases. BSS prevents colonization of infant mice with Campylobacter jejuni [ 11 and prevents diarrhea caused by enterotoxigenic Escherichia coli in human volunteers [2]. We explored the potential efficacy of BSS for prophylaxis and treatment of C. parvum diarrhea. MATERIALS AND METHODS. C. parvum oocysts were obtained and prepared as described [3]. First, 41 severe combined immunodeficiency (scid) mice were randomized to receive either diluent control (0.1 M HCI adjusted to pH 7.0 with 1 M NaOH) or BSS (Procter and Gamble, 1 mg in 10 11) by suckling every 12 h beginning 48 h before infection. All mice were infected with 2 x lo6 C. parvum oocysts by suckling at 5 7 d of age. Prophylaxis continued until 48 h postinfection, when all animals were killed. Histopathologic specimens were scored [4] under blinded conditions. To determine the in vitro activity of BSS against C. parvum, oocysts (1 x lo6) were incubated in phosphate-buffered saline (PBS), 0.1 M NaOH, simulated gastric juice (SGJ: 0.1% pepsin, 0.1% 25 mM SSYSGJ