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Volume 10, Number 10—October 2004

Dihydropteroate Synthase Gene Mutations in Pneumocystis and Sulfa Resistance

Laurence Huang*Comments to Author , Kristina Crothers*, Chiara Atzori†, Thomas Benfield‡, Robert Miller§, Meja Rabodonirina¶, and Jannik Helweg-Larsen#
Author affiliations: *University of California San Francisco, San Francisco, California, USA; †Luigi Sacco Hospital, Milan, Italy; ‡HS Rigshospitalet, Copenhagen, Denmark; §University College London, London, United Kingdom; ¶Hôspital de la Croiz-Rousse, Lyon, France; #Hvidovre University Hospital, Copenhagen, Denmark

Main Article

Table 3

Association between DHPS gene mutations and important clinical outcomesa

Author (y) (ref) PCP cases, no. DHPS mutations, no. Increased death rate? Increased PCP treatment failure? Comments
Kazanjian (1998) (19) 27 7 NA NA Both patients with DHPS mutations who were treated with TMP-SMX responded to treatment.
Mei (1998) (37) 2 2 NA NA 2 patients with DHPS mutations were treated with TMP-SMX: 1 did not respond to TMP-SMX (but responded to pentamidine); 1 responded to TMP-SMX.
Helweg-Larsen (1999) (20) 144 29 Yesb
3 months NA DHPS mutation was an independent predictor associated with increased deaths (OR = 3.1, p = 0.01).
19 patients with DHPS mutations were treated with TMP-SMX: 7 died; 12 (63%) responded and survived.
Ma (1999) (21) 37 13 No NA
Kazanjian (2000) (22) 97 42 Noc
4 weeks Yesd Patients with DHPS mutations were more likely (RR = 2.1, p = 0.01) to fail TMP-SMX or dapsone-containing treatment. Nevertheless, 15 (71%) of 21 patients with DHPS mutations who were treated with TMP-SMX or dapsone-containing regimen responded to treatment.
Takahashi (2000) (38) 22 4 NA Yes All 4 patients with DHPS mutations who were treated with TMP-SMX did not respond to treatment.
Navin (2001) (39) 136 97 Noe weeks Nof 66 patients with DHPS mutations were treated with TMP-SMX: 56 (85%) responded.
Visconti (2001) (24) 20 8 NA No 1 of 3 patients with DHPS mutations did not respond to TMP-SMX treatment.
Ma (2002) (25) 107 9 Nog
4 weeks No

aDHPS, dihydropteroate synthase; PCP, Pneumocystis pneumonia; TMP-SMX, trimethoprim-sulfamethoxazole; NA, not available.
bAssessed at 3 months.
cAssessed at 4 weeks.
dDefined as the following: a) deterioration after 7 days of therapy (worsening clinical features or gas exchange parameters—alveolar-arterial O2 gradient increase >20 mm Hg from baseline—when available); b) failure of clinical findings to improve after 10 days of therapy; c) physician perception of failure.
eAssessed at 6 weeks. Results were similar whether deaths were defined as from all cause or restricted to cases in which PCP was the primary cause of death.
fPCP treatment response defined as the following: a) patient completed full course of initial treatment and responded; b) patient responded sufficiently to be discharged on oral medication; c) patient responded to initial treatment but was given another medication because of adverse effects. Results were similar when analysis was restricted to patients who had received at least 7 days of initial PCP treatment.
gAssessed at 4 weeks. Deaths included were restricted to cases in which PCP was the primary cause of death.

Main Article

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