Sulfa or Sulfone Prophylaxis and Geographic Region Predict Mutations in the Pneumocystis carinii Dihydropteroate Synthase Gene
Open accessAbstract
To determine factors associated with mutations in the Pneumocystis carinii dihydropteroate synthase (DHPS) gene, a prospective study of human immunodeficiency virus (HIV)-infected patients with confirmed P. carinii pneumonia was conducted in Atlanta, Seattle, and San Francisco. Clinical information was obtained from patient interview and chart abstraction. DHPS genotype was determined from DNA sequencing. Overall, 76 (68.5%) of 111 patients had a mutant DHPS genotype, including 22 (81.5%) of 27 patients from San Francisco. In multivariate analysis, sulfa or sulfone prophylaxis and study site were independent predictors of a mutant genotype. Fourteen (53.8%) of 26 patients who were newly diagnosed with HIV infection and had never taken prophylaxis had a mutant genotype. The significance of geographic location as a risk factor for mutant genotype and the high proportion of mutant genotypes among persons never prescribed prophylaxis, including those newly diagnosed with HIV infection, provide indirect evidence that these mutations are transmitted from person to person either directly or through a common environmental source.
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The study that reported the highest proportion (48%) used both chart abstraction and patient interview as sources of clinical information regarding PCP prophylaxis.
“The study that reported the highest proportion (48%) used both chart abstraction and patient interview as sources of clinical information regarding PCP prophylaxis (23).”
From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [23]
The Patient interview and Medical chart abstraction sections confirm that the study used both sources for clinical information about PCP prophylaxis. The passages do not substantiate the claimed 48% proportion or establish that it was the highest among studies; Table 1 instead reports prophylaxis use in 71 of 111 patients (64.0%). (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeven 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 [23]
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 [23]
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 [23]
This study also used a broad definition of PCP prophylaxis, including patient report of TMP-SMX use for prophylaxis at any time in life.
“This study also used a broad definition of PCP prophylaxis, including patient report of TMP-SMX use for prophylaxis at any time in life.”
From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [23]
The specific city of residence was an independent predictor associated with the risk for Pneumocystis that contained DHPS gene mutations.
“The specific city of residence was also an independent predictor associated with the risk for Pneumocystis that contained DHPS gene mutations.”
From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [23]
Despite rigorous attempts to document TMP-SMX or dapsone use for PCP prophylaxis and with the broadest definition of prophylaxis applied, nearly half of the patients without TMP-SMX or dapsone use had evidence of DHPS mutations on their clinical PCP specimen.
“Thus, despite rigorous attempts to document TMP-SMX or dapsone use for PCP prophylaxis and with the broadest definition of prophylaxis applied, nearly half of the patients without TMP-SMX or dapsone use had evidence of DHPS mutations on their clinical PCP specimen.”
From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [23]
Among the 26 patients with a new diagnosis of HIV infection at the time PCP was diagnosed and who thus had never received PCP prophylaxis, 14 (54%) had Pneumocystis that contained DHPS gene mutations.
“Among the 26 patients with a new diagnosis of HIV infection at the time PCP was diagnosed and who thus had never received PCP prophylaxis, 14 (54%) had Pneumocystis that contained DHPS gene mutations.”
From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [23]
Patients who lived in San Francisco were five times more likely, and patients who lived in Seattle were more than three times as likely, to have mutant DHPS than patients who resided in Atlanta, even when factors including sulfonamide or dapsone PCP prophylaxis and prior PCP were controlled for.
“Patients who lived in San Francisco were five times more likely, and patients who lived in Seattle were more than three times as likely to have mutant DHPS than patients who resided in Atlanta, even when factors including sulfonamide or dapsone PCP prophylaxis and prior PCP were controlled for.”
From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [23]
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Self-citation
- Authors
- Huang, L., Beard, C. B., Creasman, J., Levy, D., Duchin, J. S., Lee, S., Pieniazek, N., Carter, J. L., del Rio, C., Rimland, D., & Navin, T. R.
- Affiliations
- San Francisco General Hospital (US)
- National Center for Infectious Diseases (US)
- Centers for Disease Control and Prevention (US)
- Emory University (US)
- Corresponding author
- Huang, Laurence
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-10
- Volume
- 182
- Issue
- 4
- Pages
- 1192-1198
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2148575872
- Cited by
- 149
- References
- 35
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 7 · 2012: 9
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- DigitalCommons@UNMC (submittedVersion, public-domain)
- Funders
- U.S. Department of Health and Human Services
- Centers for Disease Control and Prevention
- National Heart, Lung, and Blood Institute (K23HL072117)
- National Institute of Mental Health (P30MH059037)
- 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, dhps mutations, Pneumocystis carinii pneumonia, HIV infection, regional variation, drug resistance
- MeSH terms
- Adult, Analysis of Variance, Dihydropteroate Synthase, Ethnicity, Female, Genotype, Geography, Georgia, Humans, Male, Mutation, Pneumocystis, Pneumonia, Pneumocystis, San Francisco, Sulfonamides, Washington, HIV Infections, AIDS-Related Opportunistic Infections, Antibiotic Prophylaxis, Racial Groups
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