Download This is the first report of MAC pyo

This is the first report of MAC pyomyositis and skin abscesses presenting as
IRS in a patient receiving HAART. There
were previous single reports of MAC pyomyositis [5] and MAC skin abscesses [6]
in patients with AIDS during the era before HAART. Of interest, however, in both
of these earlier reports, the unusual clinical
presentations developed shortly after the
patients had started zidovudine monotherapy. We speculate that these may have
been due to IRS that was not recognized
in the pre-HAART era.
Stephen D. Lawn, Tihana A. Bicanic,
and Derek C. Macallan
Department of Infectious Diseases, Department of
Cellular and Molecular Medicine, St. George’s
Hospital Medical School, London, United Kingdom
References
1. DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflammatory reactions in HIV-1–infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med 2000; 133:
447–54.
2. Foudraine NA, Hovenkamp E, Notermans DW,
et al. Immunopathology as a result of highly
active antiretroviral therapy in HIV-1–infected
patients. AIDS 1999; 13:177–84.
3. Race EM, Adelson-Mitty J, Kriegel GR, et al.
Focal mycobacterial lymphadenitis following
initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease. Lancet
1998; 351:252–5.
4. Dworkin MS, Fratkin MD. Mycobacterium avium complex lymph node abscess after use of
highly active antiretroviral therapy in a patient
with AIDS. Arch Intern Med 1998; 158:1828.
5. Diego Miralles G, Bregman Z. Necrotizing
pyomyositis caused by Mycobacterium avium
complex in a patient with AIDS. Clin Infect Dis
1994; 18:833–4.
6. Barbaro DJ, Orcutt VL, Coldiron BM. Mycobacterium avium–Mycobacterium intracellulare
infection limited to the skin and lymph nodes
in patients with AIDS. Rev Infect Dis 1989; 11:
625–8.
Reprints or correspondence: Dr. Stephen D. Lawn, Dept. of
Infectious Diseases, Dept. of Cellular and Molecular Medicine, St. George’s Hospital Medical School, London SW17
ORE, United Kingdom ([email protected]).
Clinical Infectious Diseases 2004; 38:461–3
2004 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2004/3803-0031$15.00
Therapy for Severe
Histoplasmosis: What’s Best?
Sir—The interesting case of disseminated
histoplasmosis presented by Ayi and Smith
[1] raises several topics for consideration.
Demonstration of splenic nodules too numerous to count is somewhat unique but
not unexpected, since calcified splenic lesions are common in patients with cured
histoplasmosis. Other important issues
raised by this case include selection of antifungal therapy for severe histoplasmosis
and the role of adjunctive measures.
Despite excellent care and therapy with
high-dose amphotericin B lipid complex,
the patient died of septic shock and acute
respiratory distress syndrome (ARDS),
which poses the question: What is the best
antifungal agent for severe histoplasmosis?
Earlier studies showed that mortality rates
approach 50% among patients with AIDS
and severe histoplasmosis, usually because
of renal impairment that interfered with
aggressive administration of amphotericin
B (AmB) [2].
Accordingly, a double-blind trial was
conducted comparing liposomal AmB
with AmB deoxycholate [3]. The liposomal formulation was selected because it
was the least nephrotoxic, permitting aggressive therapy; because it achieved the
highest blood levels, in case that was important to the outcome; and because it
penetrated the CNS best, since CNS involvement is prominent in fatal cases.
Mortality was significantly lower with liposomal AmB treatment (1 of 53 patients
died, but not of histoplasmosis) than with
AmB deoxycholate treatment (3 of 24 patients died of histoplasmosis).
Unfortunately, because of cost, use of
the liposomal formulation of AmB is often
restricted, and it is not available unless
therapy with the other lipid formulations
fails or patients are intolerant of these
cheaper formulations. Whether the other
lipid formulations would work as well as
liposomal AmB is unknown, but their efficacy should not be assumed.
What about combination therapy? Al-
though there are no data for humans, my
colleagues and I have studied combination
therapy in a murine model, which showed
antagonism between AmB and fluconazole [4, 5]. Although itraconazole was not
antagonistic to AmB, outcomes with this
combination were no better than with
AmB alone. The activities of caspofungin [6, 7] and nikkomycin Z [8, 9]
against histoplasmosis are uncertain, and
use in combination with AmB cannot be
recommended.
A second issue is the role of adjunctive
therapy. Corticosteroids have been used in
conjunction with AmB in patients with
severe pulmonary histoplasmosis [10] and
appear to hasten recovery (author’s unpublished observation). Whether they
would be effective in patients with ARDS
and septic shock is unknown, but experience in patients with AIDS coinfected
with Pneumocystis carinii and Histoplasma
capsulatum suggests that the combination
can be administered safely (author’s unpublished observation). Granulocytemacrophage colony-stimulating factor
and IFN-g have demonstrated marginal
benefit in murine models [11, 12] but have
not been studied in human patients, and
use of these agents is not recommended.
L. Joseph Wheat
MiraVista Diagnostics and MiraBella Technologies
References
1. Ayi BS, Smith PW. Man with weight loss, fever,
cough, and an abnormal spleen. Clin Infect
Dis 2003; 37:805–6, 831–3.
2. Wheat L. Histoplasmosis in the acquired immunodeficiency syndrome. Current Topics in
Medical Mycology 1996; 7:7–18.
3. Johnson PC, Wheat LJ, Cloud GA, et al. Safety
and efficacy of liposomal amphotericin B
compared with conventional amphotericin B
for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med 2002; 137:
105–9.
4. LeMonte A, Washum K, Smedema M, Schnizlein-Bick C, Kohler R, Wheat LJ. Amphotericin B combined with itraconazole or fluconazole for treatment of histoplasmosis. J
Infect Dis 2000; 182:545–50.
5. Haynes RR, Connolly PA, Durkin MM, et al.
Antifungal therapy for central nervous system
CORRESPONDENCE • CID 2004:38 (1 February) • 463
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12.
histoplasmosis, using a newly developed intracranial model of infection. J Infect Dis
2002; 185:1830–2.
Graybill JR, Najvar LK, Montalbo EM, Barchiesi FJ, Luther MF, Rinaldi MG. Treatment
of histoplasmosis with MK-991 (L-743,872).
Antimicrob Agents Chemother 1998; 42:
151–3.
Kohler S, Wheat LJ, Connolly P, et al. Comparison of the echinocandin caspofungin with
amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model. Antimicrob Agents Chemother
2000; 44:1850–4.
Graybill JR, Najvar LK, Bocanegra R, Hector
RF, Luther MF. Efficacy of nikkomycin Z in
the treatment of murine histoplasmosis. Antimicrob Agents Chemother 1998; 42:2371–4.
Goldberg J, Connolly P, Schnizlein-Bick C, et
al. Comparison of nikkomycin Z with amphotericin B and itraconazole for treatment
of histoplasmosis in a murine model. Antimicrob Agents Chemother 2000; 44:1624–9.
Kataria YP, Campbell PB, Burlingham BT.
Acute pulmonary histoplasmosis presenting as
adult respiratory distress syndrome: effect of
therapy on clinical and laboratory features.
South Med J 1981; 74:534–7.
Clemons KV, Lutz JE, Stevens DA. Efficacy of
interferon-gamma and amphotericin B for the
treatment of systemic murine histoplasmosis.
Microbes Infect 2001; 3:3–10.
Deepe GS Jr, Gibbons R. Recombinant murine
granulocyte-macrophage colony-stimulating
factor modulates the course of pulmonary histoplasmosis in immunocompetent and immunodeficient mice. Antimicrob Agents Chemother 2000; 44:3328–36.
Reprints or correspondence: Dr. L. Joseph Wheat, MiraVista
Diagnostics, 4444 Decatur Blvd., Ste. 300, Indianapolis, IN
46241 ([email protected]).
Clinical Infectious Diseases 2004; 38:463–4
2004 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2004/3803-0032$15.00
464 • CID 2004:38 (1 February) • CORRESPONDENCE