ArticleInfection2017
Low prevalence of DHFR and DHPS mutations in Pneumocystis jirovecii strains obtained from a German cohort.
Article in Infection, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Molecular Study ofJournal of fungi (Basel, Switzerland) · 2024Article
- Molecular Analysis of Dihydropteroate Synthase Gene Mutations inInternational journal of molecular sciences · 2023Article
- Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications.The Journal of antimicrobial chemotherapy · 2022Review
- Genetic Polymorphisms ofPolish journal of microbiology · 2022Article
- Update on Dihydropteroate Synthase (DHPS) Mutations inJournal of fungi (Basel, Switzerland) · 2021Review
- Review
- Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium.Antibiotics (Basel, Switzerland) · 2020Review
- Review
- Consensus Multilocus Sequence Typing Scheme forJournal of fungi (Basel, Switzerland) · 2020Review
- Article
- Genetic polymorphisms associated with treatment failure and mortality in pediatric Pneumocystosis.Scientific reports · 2019Article
- Prevalence and genotyping of Pneumocystis jirovecii in renal transplant recipients-preliminary report.Parasitology research · 2019Article
- Therapy and Management ofJournal of fungi (Basel, Switzerland) · 2018Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of immunocompromised individuals. A combination of trimethoprim-sulfamethoxazole is widely used for prophylaxis and treatment of PCP. Polymorphisms in the drug targets, the dihydropteroate synthase (DHPS) or the dihydrofolate reductase (DHFR) are presumably a reason for treatment failure.
methodsWe retrospectively examined the prevalence of DHPS and DHFR mutations in Pneumocystis jirovecii isolates obtained from HIV-infected and non-HIV-infected PCP patients. DHFR and DHPS genes were amplified using semi-nested PCR followed by sequencing. Obtained data were correlated with clinical findings.
resultsSequencing of the DHPS gene was achieved in 81 out of 128 isolates (63%), the DHFR-gene was successfully sequenced in 96 isolates (75%). The vast majority of DHFR and DHPS sequences were either wild-type or showed synonymous single nucleotide polymorphisms. Only one sample contained a double mutation at DHPS codon 55 and codon 57 which was associated with treatment failure in some studies. No linkage of treatment failure to a DHFR or DHPS genotype was observed. In our cohort, 35 of 95 Patients (37%) were HIV-positive and 60 (63%) were HIV-negative. The overall mortality rate was 24% with a much higher rate among non-HIV patients.
conclusionDHPS and DHFR mutations exist but are infrequent in our cohort. The contribution of gene polymorphisms to treatment failure needs further research. In immunocompromised HIV-negative patients PCP is associated with high mortality rates. Prophylactic treatment is warranted in this patient subset.
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