Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-28
pubmed:abstractText
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of variants with reduced sulfa susceptibility. The present study examined the prevalence of DHPS mutations in P. jirovecii strains isolated from South African patients with PCP. P. jirovecii infection was investigated by immunofluorescence microscopy and quantitative real-time PCR with respiratory specimens from 712 patients (93% of whom were >15 years of age) with suspected PCP consecutively received for the detection of P. jirovecii over 1 year. PCR amplification and sequencing of the DHPS fas gene was attempted with DNA from the P. jirovecii-positive samples. P. jirovecii infection was confirmed by immunofluorescence microscopy in 168/712 (24%) of the patients. Carriage of the fungus was revealed by real-time PCR in 17% of the patients with negative microscopy results. The P. jirovecii fas gene was successfully amplified from specimens from 151 patients and sequenced. Mutations resulting in the Thr55Ala and/or Pro57Ser amino acid substitution were detected in P. jirovecii strains from 85/151 (56%) patients. The high frequency of PCP episodes with P. jirovecii harboring DHPS mutations in South Africa indicates that populations of this fungus are evolving under the considerable selective pressure exerted by sulfa-containing antibiotics. These results, similar to previous observations of sulfa drug resistance in bacterial populations, underscore the importance of the rational use of sulfa medications either prophylactically against PCP or for the treatment of other infections.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1098-660X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2016-21
pubmed:dateRevised
2011-3-3
pubmed:meshHeading
pubmed-meshheading:20351205-Adolescent, pubmed-meshheading:20351205-Adult, pubmed-meshheading:20351205-Aged, pubmed-meshheading:20351205-Aged, 80 and over, pubmed-meshheading:20351205-Child, pubmed-meshheading:20351205-Child, Preschool, pubmed-meshheading:20351205-DNA, Fungal, pubmed-meshheading:20351205-Dihydropteroate Synthase, pubmed-meshheading:20351205-Female, pubmed-meshheading:20351205-Fungal Proteins, pubmed-meshheading:20351205-Humans, pubmed-meshheading:20351205-Infant, pubmed-meshheading:20351205-Male, pubmed-meshheading:20351205-Microscopy, Fluorescence, pubmed-meshheading:20351205-Middle Aged, pubmed-meshheading:20351205-Mutation, Missense, pubmed-meshheading:20351205-Pneumocystis jirovecii, pubmed-meshheading:20351205-Pneumonia, Pneumocystis, pubmed-meshheading:20351205-Polymerase Chain Reaction, pubmed-meshheading:20351205-Sequence Analysis, DNA, pubmed-meshheading:20351205-South Africa, pubmed-meshheading:20351205-Sputum, pubmed-meshheading:20351205-Young Adult
pubmed:year
2010
pubmed:articleTitle
High prevalence of dihydropteroate synthase mutations in Pneumocystis jirovecii isolated from patients with Pneumocystis pneumonia in South Africa.
pubmed:affiliation
Department of Parasitology, Mycology, and Environmental Microbiology, Swedish Institute for Infectious Disease Control, Solna, Sweden. leigh.dini@smi.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't