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      A Four-Center Retrospective Study of the Efficacy and Toxicity of Low-Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Pneumonia in Patients without HIV Infection

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          ABSTRACT

          The dose of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) infection has not been verified. The aim of this study was to investigate the efficacy and toxicity of a low-dose TMP-SMX regimen in such patients. A retrospective study was conducted in four hospitals. We reviewed the medical records of patients with PCP but not HIV (non-HIV-PCP) who were treated with TMP-SMX between 2003 and 2016. The patients were divided into conventional-dose (TMP, 15 to 20 mg/kg/day) and low-dose (TMP, <15 mg/kg/day) groups after patients who received high-dose (TMP, >20 mg/kg/day) treatment were excluded. Grouping was done according to a correction dose, which was based on renal function. Eighty-two patients had non-HIV-PCP. The numbers of patients who received high-, conventional-, and low-dose treatments were 5, 36, and 41, respectively. Kaplan-Meier analysis for death associated with PCP showed no statistically significant difference in survival rates between the conventional- and low-dose groups. Ninety-day cause-specific mortality rates were 25.0% and 19.5% in the conventional-dose and low-dose groups ( P = 0.76), respectively. Adverse events that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events (version 4.0) (National Cancer Institute, 2010) were 41.7% and 17.1% in the conventional-dose and low-dose groups ( P = 0.02), respectively. Moreover, vomiting ( P = 0.03) and a decrease in platelet count ( P = 0.03) occurred more frequently in the conventional-dose group. Treatment of non-HIV-PCP with low-dose or conventional-dose TMP-SMX produces comparable survival rates; however, the low-dose regimen is better tolerated and associated with fewer adverse effects.

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          Most cited references 21

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          Pneumocystis pneumonia.

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            AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study.

            To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era. A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S. HIV clinics. We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994-2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period. Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/microl) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994-1997, 1998-2002, and 2003-2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003-2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% opportunistic illness events occurred at CD4 cell counts at least 200 cells/microl. Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003-2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/microl.
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              Diagnostic accuracy of serum 1,3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis.

              Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP.
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                Author and article information

                Journal
                Antimicrobial Agents and Chemotherapy
                Antimicrob. Agents Chemother.
                American Society for Microbiology
                0066-4804
                1098-6596
                November 22 2017
                December 2017
                December 2017
                September 11 2017
                : 61
                : 12
                Article
                10.1128/AAC.01173-17
                © 2017
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