Mutations in dihydropteroate synthase gene of Pneumocystis carinii in HIV patients with Pneumocystis carinii pneumonia.
Abstract
The purpose of this study was to determine whether dihydropteroate synthase gene (DHPS) mutations were associated with the failure of sulpha/sulphone drugs used as prophylaxis agents in HIV infected patients. Results suggested that DHPS mutations were significantly associated with failure of anti-Pneumocystis carinii sulphone prophylaxis (P=0.031). An increasing number of mutant P. carinii strains have been isolated from patients no longer having prophylaxis. There was no statistically significant difference in severity or outcome of the pneumonia caused by wild-type or mutant DHPS. Moreover, two of the three patients with mutant P. carinii pneumonia (PCP) were successfully treated with sulpha drugs. We think that P. carinii drug-resistance could be an emerging problem for immunocompromised patients including those with HIV infection.
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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 [24]
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 [24]
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 [24]
In Visconti (2001), 1 of 3 patients with DHPS mutations did not respond to TMP-SMX treatment.
“1 of 3 patients with DHPS mutations did not respond to TMP-SMX treatment.”
From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [24]
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Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance
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- Authors
- Visconti, E., Ortona, E., Mencarini, P., Margutti, P., Marinaci, S., Zolfo, M., Siracusano, A., & Tamburrini, E.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Istituto Superiore di Sanità (IT)
- Corresponding author
- Tamburrini, Enrica
- Venue
- International Journal of Antimicrobial Agents
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 18
- Issue
- 6
- Pages
- 547-551
- ISSN
- 0924-8579 (ISSN-L)
- OpenAlex
- W1989776442
- Cited by
- 50
- References
- 18
- Citations by year
- 2022: 1 · 2021: 1 · 2020: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 4
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Antimicrobial Agents (publishedVersion)
- PubMed (publishedVersion)
- 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, dihydropteroate synthase, dhps mutations, Pneumocystis carinii pneumonia, HIV infection, prophylaxis failure, drug resistance, immunocompromised patients
- MeSH terms
- Adult, Dihydropteroate Synthase, Female, Humans, Male, Middle Aged, Mutation, Pneumocystis, Pneumonia, Pneumocystis, Sulfones, HIV Infections, Treatment Failure, Drug Resistance, Bacterial
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