AIDS-associated Pneumocystis Carinii Pneumonia Research Articles

Prognostic Markers of Short-term Mortality in AIDS-Associated Pneumocystis carinii Pneumonia

Since 1990, corticosteroids have been recommended as adjunctive therapy for patients with AIDS-associated Pneumocystis carinii pneumonia (PCP) and respiratory failure. We hypothesized that the natural course of AIDS-associated PCP has changed in the era of adjunctive corticosteroid therapy. To study variables obtained on hospital admission for possible prognostic value of short-term (3-month) outcome of PCP. Prospective observational study of 176 consecutive HIV-1-infected individuals with PCP between 1990 and 1999. Cox proportional-hazards regression models. Univariate analysis showed that age, one or more prior episodes of PCP, use of antimicrobial therapy other than trimethoprim-sulfamethoxazole (TMP-SMZ), use of PCP prophylaxis at diagnosis, and culture of cytomegalovirus (CMV) in BAL predicted progression to death within 3 months. After adjustment, age (relative risk [RR], 4.1; 95% confidence interval [CI], 1.8 to 9.3), initial antimicrobial therapy other than TMP-SMZ (RR, 3.1; 95% CI, 1.2 to 8.5), use of PCP prophylaxis (RR, 5.6; 95% CI, 2.2 to 14.4), and culture of CMV in BAL fluid (RR, 2.7; 95% CI, 1.3 to 5.6) remained independent predictors of a poor outcome. In contrast, neither PO(2) nor serum lactate dehydrogenase, which in earlier studies were identified as prognostic markers, were predictors of mortality. Age, initial anti-PCP therapy, use of PCP prophylaxis, and BAL CMV status may be useful predictors of outcome of PCP in patients treated in the era of adjunctive corticosteroid therapy.

Drug monitoring during the treatment of AIDS-associated Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole.

To monitor trimethoprim and sulfamethoxazole plasma levels in patients with AIDS-associated Pneumocystis carinii pneumonia. Trimethoprim-sulfamethoxazole steady-state plasma concentrations were measured by high-pressure liquid chromatography during 37 episodes of Pneumocystis carinii pneumonia in patients with AIDS. Initially, 15-23 mg/kg/day trimethoprim and 75-115 mg/kg/day sulfamethoxazole were given i.v. Assuming a therapeutic range for trimethoprim from 4 to 10 microg/ml, the doses were adjusted if trimethoprim levels were found to be outside this range. Mean concentrations were 6.7+/-3.3 g/ml for trimethoprim and 187+/-56 microg/ml for sulfamethoxazole. A widespread inter-patient range was found and could be decreased after dose adjustment. Enzyme inducing co-medication did not influence plasma concentrations. In patients with coexisting chronic liver disease, significantly increased sulfamethoxazole plasma levels were observed. A correlation could be demonstrated between serum creatinine and trimethoprim plasma levels. Adverse reactions associated with co-trimoxazole occurred during 65% of treatment periods and increased with increasing trimethoprim-sulfamethoxazole levels, as well as increasing length of treatment. Therapy only had to be prematurely discontinued in one patient. Overall mortality was 2.7% Monitoring of co-trimoxazole levels during the treatment of P. carinii pneumonia in AIDS may help in reducing the high variability of plasma-concentrations and in avoiding severe side-effects especially associated in patients with chronic liver disease or renal failure.

Neutrophil chemotactic activity in bronchoalveolar lavage fluid of patients with AIDS-associated Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) is accompanied by an acute inflammatory infiltration of the lung parenchyma. The cellular infiltrate is characterized by inflammatory cells including neutrophils, lymphocytes and macrophages. Furthermore, neutrophilia in bronchoalveolar lavage (BAL) fluid has been shown to confer a poor prognosis in PCP. We therefore investigated the potential of BAL fluid from 17 patients with PCP to induce neutrophil chemotaxis. BAL fluid from patients induced considerable neutrophil chemotactic activity compared to normal controls. Elevated levels of IL-8 were detected in patient samples as compared to controls. A specific anti-IL-8 antibody significantly reduced chemotactic activity of patient samples by more than 50%. In conclusion, IL-8 appears to be a significant participant of neutrophil chemotaxis in AIDS-associated PCP, and may participate in the recruitment of neutrophils to the lung during PCP.

Adverse Events Associated with Trimethoprim-Sulfamethoxazole and Atovaquone during the Treatment of AIDS-Related Pneumocystis carinii Pneumonia

Atovaquone was compared to trimethoprim-sulfamethoxazole (TMP-SMZ) for the relationship of time receiving therapy, plasma drug concentrations, and incidence of adverse reactions in patients with AIDS-associated Pneumocystis carinii pneumonia. Treatment-limiting adverse events occurred in 9% of atovaquone-treated patients and 24% of TMP-SMZ-treated patients. Adverse events usually did not occur before day 7 for either treatment. Only the incidence of rash increased with increasing plasma concentrations of atovaquone. The incidence of anemia, neutropenia, and azotemia increased with increasing trimethoprim plasma concentration, while other adverse events (gastrointestinal disorders, rash, fever, and liver function abnormalities) were independent of plasma drug concentration.

Low-dose co-trimoxazole for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus disease

The efficacy and tolerability of low, intermittent doses of co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole given Monday, Wednesday, Friday) for prophylaxis against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 116 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex at high risk of PCP. 92% were receiving concomitant zidovudine. 71 with previous episode(s) of PCP were followed a mean of 18·5 months (range 3-42). 45 without past PCP but with depletion of CD4 cells to <200/μl were observed for a mean of 24·2 months (range 9-40). PCP did not develop in any patient on co-trimoxazole. 33 (28%) had side-effects, mainly rash, pruritus, and nausea. 15 discontinued co-trimoxazole, but only 11 (9%), who withdrew in the first month, were clearly drug-intolerant. Thus, low-dose, thrice weekly co-trimoxazole completely prevents AIDS-associated PCP, is cost-effective, and well tolerated by more than 85% of patients. Controlled comparisons of this regimen with other prophylactic agents are warranted.

Analysis of Induced Sputum in the Diagnosis of Pneumocystis carinii Pneumonia

Sixty-two patients with possible AIDS-associated Pneumocystis carinii pneumonia (PCP) were studied to determine the diagnostic usefulness of sputum analysis and whether or not the results of sputum analysis are related to severity of disease. Induced sputum was stained with Gomori Methenamine silver and modified Wright Giemsa stains. Indicators of disease severity were: extent of chest roentgenographic infiltrate, serum lactic dehydrogenase activity, alveolar-arterial oxygen tension difference, and total blood lymphocyte count. All patients with sputum negative for Pneumocystis underwent bronchoscopy with bronchoalveolar lavage. Sputum analysis was 71% sensitive and 100% specific for the diagnosis of PCP. The negative predictive value of sputum analysis was 48%. There was no relationship between sputum results and the severity of PCP. This study led to the conclusions that sputum analysis is a sensitive, specific, rapid, and low-cost technique for the diagnosis of PCP, and that the sensitivity of sputum analysis for the detection of PCP is not affected by the severity of PCP.

Evaluating institutional performance in AIDS-associated Pneumocystis carinii pneumonia: A risk adjustment approach

Mortality during hospital care of AIDS-associated Pneumocystis carinii pneumonia (PCP) varies as much as 3-fold among reporting institutions. Prognostic factors for death during an episode of PCP have been identified that may be useful risk adjustors for quality-of-care studies. We illustrate a risk adjustment approach to evaluating institutional performance for PCP using a pilot data set from two Southern California hospitals differing widely in crude PCP death rates (61 vs 27%). Using admission AaDO 2 hemoglobin and age in a logistic prediction model for hospital death, we found that outcomes in 90% of cases could be accurately classified. Nearly all of the “excess” mortality of the poor outcome hospital could be explained by greater pulmonary severity on admission. We discuss four conceptual issues in design of AIDS quality-of-care studies: confounding by therapeutic intention, defining relevant treatment components, determining the range of co-morbidity, and truncation of the episode of care.