Mutations in the Dihydropteroate Synthase Gene of Human‐Derived Pneumocystis carinii Isolates from Italy Are Infrequent but Correlate with Prior Sulfa Prophylaxis

Ma, Liang; Kovacs, Joseph A.; Cargnel, Antonietta; Valerio, Antonella; Fantoni, Giovanna; Atzori, Chiara

doi:10.1086/340220

Cited by 61Pneumocystis jirovecii pneumonia detection and treatmentPneumonia and Respiratory InfectionsHIV/AIDS drug development and treatment

Mutations in the Dihydropteroate Synthase Gene of Human‐Derived Pneumocystis carinii Isolates from Italy Are Infrequent but Correlate with Prior Sulfa Prophylaxis

Ma, Liang, Kovacs, Joseph A., Cargnel, Antonietta, Valerio, Antonella, Fantoni, Giovanna, Atzori, Chiara·2002·The Journal of Infectious Diseases

DOI 10.1086/340220

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Abstract

Mutations in the human-derived Pneumocystis carinii dihydropteroate synthase (DHPS) gene have been reported with increasing frequency and have been linked to prior sulfa prophylaxis and possible emergence of sulfa resistance. This study was done to examine the prevalence and clinical significance of P. carinii DHPS mutations in Italian patients. A previously described single-strand conformation polymorphism technique was used to identify P. carinii DHPS mutations in 107 patients with acquired immunodeficiency syndrome. Overall prevalence (8%) was low compared with that in other reports. Mutations were observed in 19% (6/31) of patients exposed to sulfa prophylaxis, compared with 4% (3/76) of patients not exposed to sulfa prophylaxis (P=.017). No significant association was observed between the presence of DHPS mutations and mortality, CD4 cell count, or demographic factors. The study confirms the association between DHPS mutations and prior sulfa prophylaxis and shows that the prevalence of DHPS mutations in an Italian patient population is lower than that in other populations.

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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 inPneumocystisand Sulfa Resistance (2004) · cites this paper as [25]
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 inPneumocystisand Sulfa Resistance (2004) · cites this paper as [25]
In Ma (2002), there was no increased death rate at 4 weeks associated with DHPS mutations.
“| Ma (2002) (25) | 107 | 9 | Nog 4 weeks | No | |”
From Dihydropteroate Synthase Gene Mutations inPneumocystisand Sulfa Resistance (2004) · cites this paper as [25]

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Authors: Ma, L., Kovacs, J. A., Cargnel, A., Valerio, A., Fantoni, G., & Atzori, C.
Affiliations: National Institutes of Health (US)
Luigi Sacco Hospital (IT)
ORCID: Ma, Liang
Kovacs, Joseph A.
Valerio, Antonella
Fantoni, Giovanna
Venue: The Journal of Infectious Diseases
Publisher: Oxford University Press (OUP)
Published: 2002-05-15
Volume: 185
Issue: 10
Pages: 1530-1532
ISSN: 0022-1899 (ISSN-L)
1537-6613
DOI: 10.1086/340220
OpenAlex: W2099327946
Cited by: 61
References: 14
Citations by year: 2026: 1 · 2023: 1 · 2021: 3 · 2018: 1 · 2017: 3 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 6
FWCI: 5.53
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Infectious Diseases (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, AIDS, mutation prevalence, Italy
MeSH terms: Adult, Aged, Anti-Infective Agents, Dihydropteroate Synthase, Female, Humans, Italy, Male, Middle Aged, Mutation, Pneumocystis, Pneumonia, Pneumocystis, Trimethoprim, Sulfamethoxazole Drug Combination, Bronchoalveolar Lavage

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Mutations in the Dihydropteroate Synthase Gene of Human‐Derived Pneumocystis carinii Isolates from Italy Are Infrequent but Correlate with Prior Sulfa Prophylaxis

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