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Volume 9, Number 7—July 2003
Dispatch

Sulfa Resistance and Dihydropteroate Synthase Mutants in Recurrent Pneumocystis carinii Pneumonia

Aimable Nahimana*, Meja Rabodonirina†, Jannik Helweg-Larsen‡, Isabelle Meneau*, Patrick Francioli*, Jacques Bille*, and Philippe M. Hauser*1Comments to Author 
Author affiliations: *Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; †Université Claude-Bernard, Lyon, France; ‡Hvidovre Hospital, Copenhagen, Denmark

Main Article

Table

Pneumocystis carinii DHPS and PCR-SSCP genotyping in AIDS patients with recurrent pneumoniaa

Patient no. Cityb Age Date of episode 1/
date of episode 2/
interval (mo) CD4/mm3 Prophylaxis
at PCP episodec Treatment Outcome of
treatment P. carinii
PCR-SSCP type DHPS genotyped
1
 Co
 29
 7/16/1993
 9
 D
 CO → Pe
 Success
 6
 WT
6/8/1994 (11)
 0
 P
 CO
 Success
 6
 M1
2
 Ly
 36
 1/31/1994
 58
 D
 A
 Success
 7
 M2
5/18/1995 (16)
 16
 CO
 A
 Success
 7
 M3
3
 Co
 51
 8/19/1994
 0
 No
 CO → C/Pe
 Success
 6
 WT/M1
12/23/1994 (4)
 0
 P
 T
 Success
 6
 M1
4
 Ly
 32
 11/23/1994
 75
 No
 CO
 Success
 2, 5
 WT/M3
3/23/1995 (4)
 35
 No
 CO
 Deathf
 2, 5
 M3
5
 Ly
 28
 4/19/1995
 70
 No
 A
 Success
 7, 8
 WT
3/1/1996 (11)
 98
 CO
 P
 Success
 7
 M3
6
 Co
 35
 11/16/1995
 2
 D
 P → COe
 Success
 6
 M1
5/6/1996 (6)
 1
 D
 CO
 Success
 6
 M1
7
 CF
 41
 2/3/1998
 7
 CO
 P
 Success
 6
 M3
7/22/1998 (5)
 7
 P
 C/P
 Success
 6
 M3
8
 La
 28
 11/24/1990
 53
 No
 T
 Success
 6, 10
 WT
7/29/1991 (8)
 18
 No
 CO
 Success
 7
 WT
9
 Co
 25
 12/8/1992
 0
 No
 CO
 Success
 5
 WT
11/5/1993 (11)
 0
 No
 CO
 Success
 7
 WT
10
 Co
 35
 3/22/1993
 10
 No
 CO → Pe
 Success
 18
 WT
10/28/1994 (7)
 0
 P
 CO → Pe
 Deathf
 6
 WT
11
 Ly
 23
 3/30/1994
 22
 No
 CO → Ae
 Success
 4, 7
 M3
3/28/1995 (12)
 26
 P
 D+T → Ae
 Success
 5
 M3
12
 Ly
 46
 9/21/1994
 61
 No
 CO
 Success
 15
 WT
10/21/1996 (25)
 16
 P
 P+A
 Success
 3
 WT
13
 Ly
 43
 10/12/1994
 50
 No
 CO
 Success
 1, 2
 M2
3/25/1996 (17) 5 PM/SD P+A Success 1, 3 M2

      aPCP, Pneumocystis carinii; DHPS, dihydropteroate synthase; PCR, polymerase chain reaction; SSCP, single-strand conformation polymorphism
      bCo, Copenhagen (Denmark); CF, La Chaux-de-Fonds (Switzerland); La, Lausanne (Switzerland); Ly, Lyon (France).
      cA, atovaquone; CO, cotrimoxazole; C/P, clindamycin/primaquine; D, dapsone; D+T, dapsone and trimethoprim; P, pentamidine; P+A, pentamidine and atovaquone; PM/SD (pyrimethamine/sulfadoxine inhibitors of dihydrofolate reductase (DHFR) and DHPS, respectively); T, trimetrexate (an inhibitor of DHFR).
      dWT, wild type (Thr55 Pro57); M1, mutant 1 (Ala55 Pro57); M2, mutant 2 (Thr55 Ser57); M3, mutant 3 (Ala55 Ser57 double mutant).
      eSwitch of molecules because of toxicity for patients 3, 6, and 11 and because of toxicity and treatment failure for patients 1 and 10.
      fCaused by PCP.

Main Article

1Aimable Nahimana contributed to the design of the study, analyzed the samples by polymerase chain reaction and DNA sequencing, and wrote the draft of the manuscript. Meja Rabodonirina and Jannik Helweg-Larsen reviewed medical charts and provided bronchoalveolar lavage specimens. All authors contributed to the analysis of data and writing of the paper. Philippe M. Hauser initiated and supervised all aspects of the study.

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