Genotyping of Pneumocystis jiroveci Pneumonia in Italian AIDS Patients

Abstract

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.

Dihydropteroate synthase mutations inPneumocystispneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort

“…There are however, a few potential reasons why Pneumocystis DHPS mutant infection was not associated with a significant increase in mortality in our study. First, our study had a higher prevalence of mixed DHPS infections (21%) compared to prior studies that have observed an association between DHPS mutant infection and death (prevalence range: 0–3%) [9–11]. The higher prevalence of mixed infections observed in our study may have potentially impacted a mortality difference from being observed.…”

“…Only four studies have found no association with sulfa prophylaxis and DHPS mutant. Interestingly, all four studies may have defined sulfa prophylaxis differently from those definitions used in this study: two studies did not define prophylaxis duration [17,18] while two studies defined prophylaxis as sulfa use for a minimum of one week in the six months preceding PCP diagnosis [9,19]. Furthermore, one study observed a higher prevalence of mixed infections relative to pure mutant infections [9].…”

“…Interestingly, all four studies may have defined sulfa prophylaxis differently from those definitions used in this study: two studies did not define prophylaxis duration [17,18] while two studies defined prophylaxis as sulfa use for a minimum of one week in the six months preceding PCP diagnosis [9,19]. Furthermore, one study observed a higher prevalence of mixed infections relative to pure mutant infections [9]. Combined with our study findings, this suggests that differing definitions of prophylaxis as well as differing proportions of pure mutant and mixed infections in earlier cohorts may have contributed to the conflicting associations observed in prior studies.…”

“…Second, the proportion of patients newly diagnosed with HIV was highest among the wild-type subtype. Although several studies have reported DHPS mutant infection to be associated with increased PCP severity [2,9,11,13], patients unaware of their HIV diagnosis may delay seeking medical care, presenting at a later and more advanced stage of PCP. Therefore, the higher proportion of newly diagnosed HIV-infected patients among those with the wild-type genotype may have inflated mortality in this group and masked a significant mortality difference between DHPS subtypes.…”

“…Non-uniform mortality endpoints may be partially responsible for these conflicting results. Three of nine studies examining the impact of DHPS mutations on death have found a significantly increased risk for death at four weeks [9,10] or at three months [11] while one study observed an unexpected trend towards decreased mortality at six weeks [12]. Efforts to pool or compare previously collected data have been hampered by the different mortality endpoints used in these prior studies, perhaps explaining why the clinical significance of Pneumocystis mutations remains unclear.…”