It is unclear whether patients who are unaware of their HIV infection have different severity or outcomes of Pneumocystis pneumonia (PCP) compared to patients who have been previously diagnosed with HIV. In this retrospective observational cohort study of consecutive HIV-infected patients with microscopically diagnosed PCP at San Francisco General Hospital between 1997 and 2006, 121 of 522 patients (23%) were unaware of their HIV infection prior to their diagnosis of PCP. The proportion of patients with concurrently diagnosed HIV and PCP each year remained unchanged during the study period. Patients with newly diagnosed HIV had a significantly higher alveolar-arterial oxygen gradient at presentation (median 51 versus 45 mm Hg, p=0.03), but there were no differences in mortality, frequency of mechanical ventilation, or admission to intensive care compared to patients with previously diagnosed HIV infection. In multivariate analysis, patients who reported a sexual risk factor for HIV infection were more likely to be newly diagnosed with HIV than patients who reported injection drug use as their only HIV risk factor (odds ratio = 3.14, 95% confidence interval 1.59–6.18, p = 0.001). This study demonstrates a continued need for HIV education and earlier HIV testing, particularly in patients with high-risk sexual behavior.

Background

Although the use of antiretroviral therapy has led to dramatic declines in AIDS-associated mortality, Pneumocystis pneumonia (PCP) remains a leading cause of death in HIV-infected patients.

Objectives

To measure mortality, identify predictors of mortality at time of illness presentation, and derive a PCP mortality prediction rule that stratifies patients by risk for mortality.

Methods

Observational cohort study with case note review of all HIV-infected persons with a laboratory diagnosis of PCP at San Francisco General Hospital from 1997–2006.

Results

451 patients were diagnosed with PCP on 524 occasions. In-hospital mortality was 10.3%. Multivariate analysis identified five significant predictors of mortality: age (adjusted odds ratio [AOR] per 10-year increase, 1.69; 95% confidence interval [CI] 1.08–2.65; p=0.02); recent injection drug use (AOR 2.86; 95% CI 1.28–6.42; p=0.01); total bilirubin >0.6 mg/dL (AOR 2.59; 95% CI 1.19–5.62; p=0.02); serum albumin <3 g/dL (AOR 3.63; 95% CI 1.72–7.66; p=0.001); and alveolar-arterial oxygen gradient ≥50 mm Hg (AOR 3.02; 95% CI 1.41–6.47; p=0.004). Using these five predictors, we derived a six point PCP mortality prediction rule that stratifies patients according to increasing risk of mortality: score 0–1, 4%; score 2–3, 12%; score 4–5, 48%.

Conclusions

Our PCP mortality prediction rule stratifies patients by mortality risk at the time of illness presentation and should be validated as a clinical tool.

Background

S-adenosylmethionine (SAM)1 has been suggested as a diagnostic test and surrogate marker for Pneumocystis jirovecii pneumonia (PCP) in HIV-positive patients. In this study, we report a robust hydrophilic-interaction liquid chromatography tandem mass spectrometry (LC-MS/MS) assay that can be used to quantitate serum SAM in clinical laboratories.

Methods

Proteins in serum samples were precipitated using trichloroacetic acid. The supernatant was separated after centrifugation. D3-SAM was added as the internal standard. SAM and d3-SAM were extracted using a mixed-mode cation exchange column. Extracts were dried under nitrogen and reconstituted in H2O and acetonitrile (1:9, vol:vol). HPLC-tandem mass spectrometry analysis was performed with a silica column and multiple reaction monitoring for SAM and d3-SAM.

Results

The limit of quantitation (LOQ) for SAM was 10 ng/mL. The assay was linear between 10–500 ng/mL. Intra-assay coefficient of variation (CV) was 8% and inter-assay CV was 17% at the LOQ. Turnaround time for each specimen was approximately 1 hour. Using this method, we found that serum SAM concentration was correlated with fasting status, especially methionine intake. We also measured acute and convalescent serum SAM levels of 8 HIV-positive patients with PCP and non-PCP pneumonia. SAM concentrations in convalescent samples were significantly increased compared to acute levels only in patients with PCP.

Conclusions

The LC-MS/MS method had sufficient analytical sensitivity for detecting low levels of SAM found in HIV-infected patients and can be used for quantitative measurements in a clinical laboratory. This method facilitates research and possible clinical application of SAM as a marker for PCP.

Humans may be a reservoir for this pathogen and transmit it from person to person.

The reservoir and mode of transmission of Pneumocystis jirovecii remain uncertain. We conducted a cross-sectional study of 126 San Francisco General Hospital staff in clinical (n = 103) and nonclinical (n = 23) occupations to assess whether occupational exposure was associated with immune responses to P. jirovecii. We examined antibody levels by ELISA for 3 overlapping fragments that span the P. jirovecii major surface glycoprotein (Msg): MsgA, MsgB, and MsgC1. Clinical occupation participants had higher geometric mean antibody levels to MsgC1 than did nonclinical occupation participants (21.1 vs. 8.2, p = 0.004); clinical occupation was an independent predictor of higher MsgC1 antibody levels (parameter estimate = 0.89, 95% confidence interval 0.29–1.48, p = 0.003). In contrast, occupation was not significantly associated with antibody responses to either MsgA or MsgB. Healthcare workers may have occupational exposure to P. jirovecii. Humans may be a reservoir for P. jirovecii and may transmit it from person to person.