Universität zu Köln

Suarez, Isabelle, Roderus, Lisa, van Gumpel, Edeltraud, Jung, Norma, Lehmann, Clara, Faetkenheuer, Gerd, Hartmann, Pia, Plum, Georg and Rybniker, Jan (2017). Low prevalence of DHFR and DHPS mutations in Pneumocystis jirovecii strains obtained from a German cohort. Infection, 45 (3). S. 341 - 348. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1439-0973

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Abstract

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. 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. 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. 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Suarez, Isabelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Roderus, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED van Gumpel, Edeltraud UNSPECIFIED UNSPECIFIED UNSPECIFIED Jung, Norma UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Clara UNSPECIFIED UNSPECIFIED UNSPECIFIED Faetkenheuer, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Plum, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Rybniker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-229730
DOI:	10.1007/s15010-017-1005-4
Journal or Publication Title:	Infection
Volume:	45
Number:	3
Page Range:	S. 341 - 348
Date:	2017
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1439-0973
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DIHYDROPTEROATE SYNTHASE GENE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CELL TRANSPLANT RECIPIENTS; CARINII-PNEUMONIA; DIHYDROFOLATE-REDUCTASE; NON-HIV; TRIMETHOPRIM-SULFAMETHOXAZOLE; HEMATOLOGICAL MALIGNANCIES; RESISTANCE; GENOTYPES Multiple languages Infectious Diseases Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22973