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Volume 10, Number 10—October 2004
Perspective

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 2

Association between sulfonamide or sulfone for PCP prophylaxis and DHPS gene mutationsa

Author 
(y) (ref) PCP cases, no. Location 
(time period), country Prophylaxisb definition (source of information) DHPS mutations 
among persons 
using prophylaxis 
N (%) DHPS mutations 
among persons not using prophylaxis 
N (%) p value
Kazanjian (1998) (19) 27 
(20 HIV-infected) Ann Arbor, MI 
(1991–1997), USA 5/7 (71)c 2/20 (10)c 0.0032
Indianapolis, IN 
(1976–1997), USA At least 1 out of 4 months preceding PCP (chart) 5/7 (71)d 2/13 (15)d 0.022
Helweg-Larsen (1999) (20) 152 Copenhagen 
(1989–1999), Denmark Exposuree (chart) 18/29 (62) 13/123 (11) < 0.0001
Prophylaxisf (chart) 5/7 (71)g 15/125 (12) 0.01
Ma (1999) (21) 37 (26 HIV-infected) Bethesda, MD 
(1985–1998), USA Any (chart) 11/14 (79) 2/18 (11) < 0.001
Kazanjian (2000) (22) 97 Denver, CO, Indianapolis, IN, Boston, MA, Detroit, MI (1991–1997), USA At least 1 out of 4 months preceding PCP (chart) 28/37 (76) 14/60 (23) < 0.001
Huang (2000) (23) 111 Atlanta, GA, Seattle, WA, San Francisco, CA (1996–1999), USA Ever (interview), Any in the 
3 months preceding PCP (chart and interview) 57/71 (80) 19/40 (48) < 0.001
Visconti (2001) (24) 20 Rome (1992–1997), Italy (Chart) 4/5 (80) 4/15 (27) 0.031
Ma (2002) (25) 107 Milan (1994–2001), Italy Any in the 6 months preceding PCP (chart) 6/31 (19) 3/76 (4) 0.017
Costa (2003) (29) 89 (83 HIV-infected) Lisbon (1994–2001), Portugal Prophylaxish
Exposurei 6/17 (35) 18/72 (25) 0.39
Nahimana (2003) (30) 158 
(120 HIV-infected) Lyon (1993–1996), France Prophylaxisj 16/20 (80) 41/138 (30) < 0.001

aPCP, Pneumocystis pneumonia; dihydropteroate synthase (DPHS); TMP-SMX, trimethoprim-sulfamethoxazole.
bProphylaxis refers to persons using TMP-SMX or dapsone who met the specific criteria described.
cThe seven specimens with DHPS gene mutations were from 1995 to 1997.
dAnalysis restricted to 20 HIV-infected persons.
eExposure, continuous use for at least 1 week at any time after the diagnosis of HIV infection.
fProphylaxis at least 8 weeks preceding PCP.
gAnalysis restricted to patients receiving TMP-SMX or dapsone prophylaxis versus no prophylaxis.
hProphylaxis, adherence to the same regimen for a minimum of 2 months preceding PCP.
iExposure, use for at least 1 week in the 6 months preceding PCP.
jProphylaxis 3 months preceding PCP. Includes patients who received pyrimethamine/sulfadoxine for PCP prophylaxis.

Main Article

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