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Cited by 164Pneumocystis jirovecii pneumonia detection and treatmentPneumonia and Respiratory InfectionsHIV/AIDS drug development and treatment

Pneumocystis carinii Mutations Are Associated with Duration of Sulfa or Sulfone Prophylaxis Exposure in AIDS Patients

Kazanjian, Powel, Armstrong, Wendy, Hossler, Paul A., Burman, William, Richardson, James, Lee, Chao‐Hung, Crane, Lawrence, Katz, Joel +1 more·2000·The Journal of Infectious Diseases
DOI 10.1086/315719
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Abstract

This study was conducted to determine whether Pneumocystis carinii dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers were amplified, using polymerase chain reaction (PCR), and sequenced. Mutations were observed in 76% of isolates from patients exposed to sulfa or sulfone prophylaxis compared with 23% of isolates from patients not exposed (P=.001). Duration of prophylaxis increased the risk of mutations (relative risk [RR] for each exposure month, 1.06; P=.02). Twenty-eight percent of patients with mutations failed sulfa or sulfone treatment; mutations increased the risk of sulfa or sulfone treatment failure (RR, 2.1; P=0.01). Thus, an increased duration of sulfa or sulfone prophylaxis increases the chance of developing a P. carinii mutation. The majority of patients with mutations respond to sulfa or sulfone therapy.

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Crossref · 10.1086/315719

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  • Sulfa medications appear to exert selective pressure on Pneumocystis, as the DHPS gene is more likely to display mutations in highly conserved regions in patients with PCP who have previously been exposed to sulfa medications.

    “Sulfa medications appear to exert selective pressure on Pneumocystis (18), as the DHPS gene is more likely to display mutations in highly conserved regions in patients with PCP who have previously been exposed to sulfa medications (19–25).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [22]

  • Seven of the nine studies found that most HIV-infected patients with a diagnosis of PCP who had been prescribed TMP-SMX or dapsone for PCP prophylaxis had Pneumocystis that contained DHPS mutations (range 19%-80%).

    “Nevertheless, seven of the nine studies found that most HIV-infected patients with a diagnosis of PCP who had been prescribed TMP-SMX or dapsone for PCP prophylaxis had Pneumocystis that contained DHPS mutations (range 19%–80%, Table 2) (19–24,30).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [22]

  • Several studies have consistently demonstrated a significant association between the use of TMP-SMX or dapsone for PCP prophylaxis in HIV-infected persons and the presence of DHPS gene mutations.

    “Several studies have consistently demonstrated a significant association between the use of TMP-SMX or dapsone for PCP prophylaxis in HIV-infected persons and the presence of DHPS gene mutations (Table 2) (19–25,30).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [22]

  • These DHPS gene mutations were rarely found in clinical isolates before the early 1990s.

    “These DHPS gene mutations were rarely found in clinical isolates before the early 1990s (19,20,22).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [22]

  • In univariate analysis, PCP patients with Pneumocystis containing DHPS gene mutations had a greater than twofold increased risk for treatment failure with TMP-SMX or dapsone plus trimethoprim compared to patients with wild-type DHPS.

    “In univariate analysis, PCP patients who had Pneumocystis that contained DHPS gene mutations had a greater than twofold increased risk for treatment failure with one of these regimens, compared to patients with the wild-type DHPS.”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [22]

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Authors
Kazanjian, P., Armstrong, W., Hossler, P. A., Burman, W., Richardson, J., Lee, C., Crane, L., Katz, J., & Meshnick, S. R.
Affiliations
  • University of Michigan (US)
  • Denver Health Medical Center (US)
  • Indiana University Health (US)
  • Wayne State University (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Kazanjian, Powel
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2000-08
Volume
182
Issue
2
Pages
551-557
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1086/315719
OpenAlex
W2107137005
Cited by
164
References
23
Citations by year
2025: 1 · 2024: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 8
FWCI
8.82
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ai031775-05)
  • National Institute of Allergy and Infectious Diseases (R01-AI 31775)
Topics
  • Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
Pneumocystis carinii, Pneumocystis carinii pneumonia, AIDS, dihydropteroate synthase, drug resistance, treatment failure, prophylaxis duration, antifolate therapy
MeSH terms
Acquired Immunodeficiency Syndrome, Adult, Dapsone, Dihydropteroate Synthase, Female, Humans, Male, Middle Aged, Mutation, Pneumocystis, Pneumonia, Pneumocystis, Sulfones, United States, Trimethoprim, Sulfamethoxazole Drug Combination

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