ABSTRACT
Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.
ABSTRACT
Objective To summarize the clinical features of encephalopathy caused by Toxoplasma gondii in AIDS patients for improving clinical diagnosis and treatment of such cases. Methods The clinical data of patients with AIDS and toxoplasmic encephalopathy were collected retrospectively. The prevalence of toxoplasmic encephalopathy in AIDS patients was analyzed. The anti-toxoplasmic efficacy of trimethoprim-sulfamethoxazole (SMZ-TMP) plus azithromycin was reviewed. Results Toxoplasmic encephalopathy was reported in about 10.0％ of the AIDS patients complicated with central nervous system disorder. Headache, fever, and limb movement disorder were the most common symptoms. Head CT/MRI scan showed that 89.5％ of the patients had multiple lesions, mostly in the parietal lobe, temporal lobe and basal ganglia. Enhancement scan revealed thatcircular enhanced foci in 76.9％ of the patients, nodular enhanced foci in 59.0％ of the patients, and surrounding edema in 79.5％ of the patients. The mean CD4+ T lymphocytes was (65.8±59.3)/μL.Anti-toxoplasmic IgG was positive in 50.0％ of the patients, higher than that of IgM (11.5％) (P＜0.05). The positive rate of IgG antibody specific for Toxoplasma gondii tested by ELISA was higher than that detected by rapid colloidal gold immunoassay (P＜0.05). Increased cerebrospinal fluid pressure was found in 42.6％ of the patients. Increased protein in CSF was identified in 66.0％ of the patients. Most (84.2％) patients were improved after treatment with SMZ-TMP plus azithromycin. Conclusions Toxoplasmic encephalopathy is one common central nervous system disease in AIDS patients. The clinical symptoms are nonspecific. There are some features in imaging examination. Low count of CD4+ T lymphocytes makes patients more susceptible to Toxoplasma infection. The anti-toxoplasmic IgG antibody may be helpful for diagnosis. The results of cerebrospinal fluid examination are not specific. SMZ-TMP in combination with azithromycin promises good treatment effect.