Pneumocystis jirovecii Dihydropteroate Synthase Gene Mutations and Human Immunodeficiency Virus-Associated Pneumocystis Pneumonia

2006 ◽  
Vol 53 (s1) ◽  
pp. S114-S116 ◽  
Author(s):  
LAURENCE HUANG ◽  
DAVID A. WELSH ◽  
ROBERT F. MILLER ◽  
C. BEN BEARD ◽  
GENA G. LAWRENCE ◽  
...  
AIDS ◽  
2005 ◽  
Vol 19 (8) ◽  
pp. 801-805 ◽  
Author(s):  
Kristina Crothers ◽  
Charles B Beard ◽  
Joan Turner ◽  
Gena Groner ◽  
Melissa Fox ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49991 ◽  
Author(s):  
Steve M. Taylor ◽  
Steven R. Meshnick ◽  
William Worodria ◽  
Alfred Andama ◽  
Adithya Cattamanchi ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248524
Author(s):  
Rui Li ◽  
Zhiyong Tang ◽  
Fu Liu ◽  
Ming Yang

Background Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine. Methods A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported. Results Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03). Conclusions TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.


2000 ◽  
Vol 38 (9) ◽  
pp. 3161-3164 ◽  
Author(s):  
Takashi Takahashi ◽  
Noriaki Hosoya ◽  
Tokiomi Endo ◽  
Tetsuya Nakamura ◽  
Hiroyuki Sakashita ◽  
...  

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis(P. carinii) strains isolated from 24 patients withP. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 infection (n= 4) or malignant lymphoma (n = 2). This frequency was almost the same as those reported in Denmark and the United States. None of the six patients whose isolates had DHPS mutations were recently exposed to sulfa drugs before they developed the current episode of PCP, suggesting that DHPS mutations not only are selected by the pressure of sulfa agents but may be incidentally acquired. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n = 4 [100%] versus n = 2 [11.1%]; P = 0.002). Our results thus suggest that DHPS mutations may contribute to failures of co-trimoxazole treatment for PCP.


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