Genotyping of Pneumocystis jiroveci pneumonia in Italian AIDS patients. Clinical outcome is influenced by dihydropteroate synthase and not by internal transcribed spacer genotype.
BACKGROUND
Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P jiroveci pneumonia (PcP).


METHODS
Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review.


RESULTS
High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028).


CONCLUSIONS
The present data suggest the absence of a correlation between P jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features.
Valerio
Antonella
A
II Department of Infectious Diseases, Luigi Sacco Hospital, Milan, Italy
Tronconi
Elisa
E
Mazza
Francesca
F
Fantoni
Giovanna
G
Atzori
Chiara
C
Tartarone
Federica
F
Duca
Piergiorgio
P
Cargnel
Antonietta
A
D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology*; D000328:Adult; D000368:Aged; D021901:DNA, Intergenic / Q000235:genetics; D004094:Dihydropteroate Synthase / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005814:Genes, Viral; D006678:HIV; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D045363:Pneumocystis carinii / Q000235:genetics*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013045:Species Specificity; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics*
D021901:DNA, Intergenic; D014764:Viral Proteins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004094:Dihydropteroate Synthase