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Low prevalence of DHFR and DHPS mutations in Pneumocystis jirovecii strains obtained from a German cohort.

Low prevalence of DHFR and DHPS mutations in Pneumocystis jirovecii strains obtained from a German cohort.
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Suárez I, Roderus L, van Gumpel E, Jung N, Lehmann C, Fätkenheuer G, Hartmann P, Plum G, Rybniker J,


Suárez I, Roderus L, van Gumpel E, Jung N, Lehmann C, Fätkenheuer G, Hartmann P, Plum G, Rybniker J, (click to view)

Suárez I, Roderus L, van Gumpel E, Jung N, Lehmann C, Fätkenheuer G, Hartmann P, Plum G, Rybniker J,

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Infection 2017 03 16() doi 10.1007/s15010-017-1005-4

Abstract
BACKGROUND
Pneumocystis 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.

METHODS
We 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.

RESULTS
Sequencing 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.

CONCLUSION
DHPS 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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