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1.  Pneumocystis Pneumonia in Hospitalized Patients; A Detailed Examination of Symptoms, Management, and Outcomes in HIV-infected and HIV-uninfected Persons 
Background
Pneumocystis jiroveci pneumonia is a life-threatening infection for immunocompromised individuals. There are robust data and clear guidelines for prophylaxis and treatment of HIV-related Pneumocystis jiroveci pneumonia (HIV-PCP), yet few data and no guidelines for non-HIV related Pneumocystis pneumonia (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP.
Methods
We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP.
Results
Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, p=0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 vs 1.1 days, P<0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1,066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, p=0.39) and 90-day mortality (41% vs. 28%, p=0.20) were detected.
Conclusions
Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empiric therapy for PCP.
doi:10.1111/j.1399-3062.2012.00739.x
PMCID: PMC3889465  PMID: 22548840
Pneumocystis Pneumonia; Transplant; Infectious Complications
2.  Utility of bronchoscopy with bronchoalveolar lavage in diagnosing pulmonary infection in hospitalized patients with underlying malignancy 
Objectives:
To evaluate the clinical utility of bronchoscopy with bronchoalveolar lavage (BAL) for diagnosing pulmonary infection in patients with underlying malignancy and to evaluate the impact of positive microbiology results on antimicrobial therapy.
Design:
Retrospective chart review.
Setting:
University-affiliated downtown teaching hospital in Toronto.
Patient population:
All patients who underwent bronchoscopy with BAL from November 1990 to September 1992.
Results:
One hundred and thirty-nine BALs were performed, of which 82 (59%) were positive for microorganisms. These 82 charts were reviewed. The main underlying diagnosis was hemotogenous malignancy (70 of 82). Primary indiction for bronchoscopy was the presence of pulmonary symptoms with or without radiographic abnormality. Common organisms identified were fungi (n=50), primarily Candida albicans and cytomegalovirus (CMV) (27), and 16 ‘usual’ pathogens. Less common were herpes simplex virus (six), Pneumoncystis carinii pneumonia (PCP) (four), Legionella pneumoniae and Mycoplasma pneumoniae (one each). Eighty-seven per cent of patients were on broad spectrum antibiotics at the time of bronchoscopy. Although antiibiotic therapy was altered postbronchoscopy in 47 of the 82 cases, only 26 instances could be directly attributed to the results of BAL. Pathogens that commonly initiated specific therapy were CMV (16 of 27) and PCP (three of four). Diagnostic yield was highest in allogenic bone marrow transplant recipients (BMT). They comprised only 49% (40 of 82) of the cases but accounted for 85% (22 of 26) of those whose therapy was directly altered by the results of BAL. Of these 22 cases, 20 were attributed to the isolation of CMV.
Conclusions:
The overall raw diagnostic yield from bronchoscopy with BAL was high at 59%. Of those with positive BAL cultures, a change in antimicrobial management occurred in 32% of cases. In a patient poulation with underlying hematogenous malignancy, particularly BMT recipients, bronchoscopy with BAL is useful for a specfic diagnosis of pulmonary infection.
PMCID: PMC3307535  PMID: 22451776
Bronchoalveolar lavage; Clinical utility; Pulmonary infection
3.  Intravenous Pentamidine Is Effective as Second Line Pneumocystis Pneumonia Prophylaxis in Pediatric Oncology Patients 
Pediatric blood & cancer  2008;50(4):779-783.
Background
Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a life-threatening risk to oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis virtually eliminates the risk of infection; however, many patients cannot tolerate TMP-SMZ. We performed a retrospective analysis to determine the PCP breakthrough rate in pediatric oncology patients receiving intravenous pentamidine as second line PCP prophylaxis.
Procedure
We conducted a retrospective chart review of pediatric oncology patients who received intravenous pentamidine from 2001 to 2006 at our institution. The diagnosis, age and bone marrow transplant (BMT) status were determined. A subset of patients had review of their records to determine the justification for discontinuing TMP-SMZ. Children who developed symptoms of pneumonia with a clinical suspicion of PCP underwent bronchoscopy, allowing for identification of Pneumocystis.
Results
A total of 232 patients received 1,706 doses of intravenous pentamidine and no toxicities were identified. The main reasons for discontinuing TMP-SMZ were bone marrow suppression and drug allergy. Three children developed PCP, equating to a breakthrough rate of 1.3%. Two of these children had undergone BMT (1.9% breakthrough rate) and both were under the age of two (6.5% breakthrough rate).
Conclusions
The use of intravenous pentamidine as PCP prophylaxis results in a breakthrough rate of 1.3%. TMP-SMZ is the first choice for PCP prophylaxis. However, when necessary, the use of intravenous pentamidine has an acceptably low failure rate, even in high-risk BMT patients. Other options should be considered for children less than 2 years of age.
doi:10.1002/pbc.21287
PMCID: PMC4273575  PMID: 17635000
pentamidine; Pneumocystis pneumonia; prophylaxis
4.  Detection of Pneumocystis DNA in samples from patients suspected of bacterial pneumonia- a case-control study 
Background
Pneumocystis jiroveci (formerly known as P. carinii f.sp. hominis) is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised individuals. Pneumocystis jiroveci can be detected by polymerase chain reaction (PCR). To investigate the clinical importance of a positive Pneumocystis-PCR among HIV-uninfected patients suspected of bacterial pneumonia, a retrospective matched case-control study was conducted.
Methods
Respiratory samples from 367 patients suspected of bacterial pneumonia were analysed by PCR amplification of Pneumocystis jiroveci. To compare clinical factors associated with carriage of P. jiroveci, a case-control study was done. For each PCR-positive case, four PCR-negative controls, randomly chosen from the PCR-negative patients, were matched on sex and date of birth.
Results
Pneumocystis-DNA was detected in 16 (4.4%) of patients. The median age for PCR-positive patients was higher than PCR-negative patients (74 vs. 62 years, p = 0.011). PCR-positive cases had a higher rate of chronic or severe concomitant illness (15 (94%)) than controls (32 (50%)) (p = 0.004). Twelve (75%) of the 16 PCR positive patients had received corticosteroids, compared to 8 (13%) of the 64 PCR-negative controls (p < 0.001).
Detection of Pneumocystis-DNA was associated with a worse prognosis: seven (44%) of patients with positive PCR died within one month compared to nine (14%) of the controls (p = 0.01). None of the nine PCR-positive patients who survived had developed PCP at one year of follow-up.
Conclusions
Our data suggest that carriage of Pneumocystis jiroveci is associated with old age, concurrent disease and steroid treatment. PCR detection of P. jiroveci has low specificity for diagnosing PCP among patients without established immunodeficiency. Whether overt infection is involved in the poorer prognosis or merely reflects sub-clinical carriage is not clear. Further studies of P. jiroveci in patients receiving systemic treatment with corticosteroids are warranted.
doi:10.1186/1471-2334-2-28
PMCID: PMC139972  PMID: 12445330
5.  Outcomes of Moderate-to-Severe Pneumocystis Pneumonia Treated with Adjunctive Steroid in Non-HIV-Infected Patients▿† 
Antimicrobial Agents and Chemotherapy  2011;55(10):4613-4618.
While it is well-known that adjunctive corticosteroid use improves the outcome of moderate-to-severe Pneumocystis jirovecii pneumonia (PcP) in patients with human immunodeficiency virus (HIV), there are limited data on its efficacy in non-HIV-infected patients with PcP. Patients undergoing fiber-optic bronchoscopy with bronchoalveolar lavage for suspected PcP from January 2007 through December 2010 were reviewed retrospectively. We compared demographics, clinical characteristics, and outcomes in 88 non-HIV-infected patients with moderate-to-severe PcP with (n = 59) and without (n = 29) adjunctive corticosteroid use. Outcomes of PcP were assessed by respiratory failure and 30-day and 90-day all-cause mortality. Survival curves were analyzed by the Kaplan-Meier method and estimated by the log rank test. All-cause mortality of moderate-to-severe PcP at 90 days was lower in the solid-organ transplant recipients than in all other patients (6/26 [23%] versus 34/62 [55%], respectively; P = 0.006), and mortality at 30 days was lower in patients with hematologic malignancies than in all other patients (4/26 [15%] versus 24/62 [39%], respectively; P = 0.03). The outcomes of PcP were not significantly different in moderate-to-severe PcP patients with and without adjunctive corticosteroid use, regardless of recent corticosteroid use. Survival analysis of PcP patients with and without corticosteroid use by the Kaplan-Meier method also did not reveal any difference (log rank test; P = 0.81). There again was no difference within the subgroup of PcP patients with solid-organ transplants. Adjunctive corticosteroid use may not improve the outcome of moderate-to-severe PcP in non-HIV-infected patients.
doi:10.1128/AAC.00669-11
PMCID: PMC3186978  PMID: 21788460
6.  Blood (1→3)-β-D-Glucan as a Diagnostic Test for HIV-Related Pneumocystis jirovecii Pneumonia 
In a large group of HIV-infected clinical trial participants with diverse opportunistic infections, blood beta-glucan was a more sensitive noninvasive test for PCP than serum LDH; sensitivity was also higher than that frequently reported for induced sputum examinations.
(See the editorial commentary by Morris and Masur, on pages 203–204.)
Background. Improved noninvasive diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) are needed. We evaluated the test characteristics of plasma (1→3)-β-D-glucan (β-glucan) for HIV-related PCP among a large group of patients presenting with diverse opportunistic infections (OIs).
Methods. The study population included all 282 participants in AIDS Clinical Trials Group A5164, a study of early versus deferred antiretroviral therapy in conjunction with initial therapy of acute OIs. Baseline plasma samples were assayed for β-glucan, with standard assay reference values defining ≥80 pg/mL as positive. Before this analysis, diagnosis of PCP was independently adjudicated by 2 study investigators after reviewing reports from study sites.
Results. A total of 252 persons had a β-glucan result that could be analyzed, 173 (69%) of whom had received a diagnosis of PCP. Median β-glucan with PCP was 408 pg/mL (interquartile range [IQR], 209–500 pg/mL), compared with 37 pg/mL (IQR, 31–235 pg/mL) without PCP (P < .001). The sensitivity of β-glucan dichotomized at 80 pg/mL for the diagnosis of PCP was 92% (95% confidence interval [CI], 87%–96%), and the specificity was 65% (95% CI, 53%–75%); positive and negative predictive values were 85% (95% CI, 79%–90%) and 80% (95% CI, 68%–89%) respectively, based on the study prevalence of 69% of patients with PCP. Rates of abnormal lactate dehyrogenase levels did not differ significantly between those with and without PCP.
Conclusions. Blood (1→3)-β-D-glucan is strongly correlated with HIV-related PCP. In some clinical centers, this may be a more sensitive test than the induced sputum examination and could reduce the need for both bronchoscopy and empirical therapy of PCP.
doi:10.1093/cid/cir335
PMCID: PMC3165964  PMID: 21690628
7.  Granulomatous Pneumocystis jiroveci pneumonia associated with immune reconstituted HIV 
Immune reconstitution disease occurs in 10% to 25% of patients receiving highly active antiretroviral therapy, and is considered to be a risk factor for the development of granulomatous Pneumocystis jiroveci pneumonia (PCP), which is an uncommon form of pneumocystis infection. Most commonly described in HIV patients with low CD4+ counts, granulomatous PCP develops insidiously and presents with minimal symptoms. This report describes a case of granulomatous PCP involving a 40-year-old HIV-positive man, and highlights the difficulty in its diagnosis and the need to consider PCP in HIV patients when initiating therapy.
Pneumocystis jiroveci pneumonia uncommonly presents with pulmonary nodules and granulomatous inflammation. An unusual case of granulomatous P jiroveci pneumonia in an HIV patient with a CD4+ lymphocyte count of greater than 200 cells/mm3, occurring in the context of immune reconstitution with highly active antiretroviral therapy, is described. The case highlights the importance of establishing this diagnosis to institute appropriate therapy.
PMCID: PMC3267626  PMID: 22187692
HIV/AIDS; Immune reconstitution disease; Multiple pulmonary nodules; Pneumocystis jiroveci
8.  Comparison of community-acquired pneumonia requiring admission to hospital in HIV-and non-HIV-infected patients 
OBJECTIVE:
To compare community-acquired pneumonia (CAP) in hospitalized human immunodeficiency virus (HIV)-infected patients with that in hospitalized non-HIV-infected patients by assessing presenting characteristics, etiology and outcomes.
DESIGN:
Retrospective chart review.
SETTING:
A tertiary care centre in Halifax, Nova Scotia.
POPULATION STUDIED:
Thirty-two HIV-infected patients requiring hospitalization for treatment of CAP were identified from September 1991 to October 1993 and compared with 33 age-matched non-HIV-infected patients who presented with pneumonia during the same period.
MAIN RESULTS:
The two populations were comparable in age, sex and race. Fifty per cent of the HIV-infected and 20.8% of the non-HIV-infected patients had had a previous episode of pneumonia. Pneumocystis carinii pneumonia (PCP) accounted for 16 of the 32 episodes of CAP in the HIV-infected patients, while none of the non-HIV-infected patients had PCP. Pneumonia secondary to Streptococcus pneumoniae was more common in the non-HIV-infected patients (five versus one, P=0.02). Vital signs and initial PO2 did not differ between the two groups. White blood cell count was lower at admission for the HIV population (5.7×109/L versus 12.7×109/L, P=0.003). The HIV patients were more likely to undergo bronchoscopy (27.7% versus 0%, P<0.001). The length of stay in hospital, transfer to the intensive care unit and necessity for intubation were the same for both groups. The in-hospital mortality for HIV-infected patients was eight of 32 (25%) while for the non-HIV-infected patients it was none of 33 (P=0.002).
CONCLUSIONS:
Patients with HIV infection who present with CAP are more likely to have PCP, to have had a past episode of pneumonia and to die while in hospital than age- and sex-matched non-HIV-infected patients with CAP.
PMCID: PMC3327412  PMID: 22514448
Community-acquired pneumonia; Human immunodeficiency virus infection; Hospitalization
9.  Pneumocystis jirovecii Pneumonia in Tropical and Low and Middle Income Countries: A Systematic Review and Meta-Regression 
PLoS ONE  2013;8(8):e69969.
Objective
Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings.
Design
Systematic review and meta-regression.
Methods
Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies).
Results
The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p<0.0001). This was not explained by study design or diagnostic quality. Geographical area, population age, study setting and year of study also contributed to risk of PCP. Co-infection was common (444 episodes/1425 PCP cases), frequently with virulent organisms. The predictive value of symptoms, signs or simple tests in LMIC settings for diagnosis of PCP was poor. Case fatality was >30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×103/ml.
Conclusions
There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii, ubiquitous in all settings, then becomes a greater relative threat.
doi:10.1371/journal.pone.0069969
PMCID: PMC3732248  PMID: 23936365
10.  Quantitative and qualitative comparison of DNA amplification by PCR with immunofluorescence staining for diagnosis of Pneumocystis carinii pneumonia. 
Journal of Clinical Pathology  1993;46(2):140-144.
AIM: To compare the results of DNA amplification by the polymerase chain reaction (PCR) with immunofluorescence staining for detecting Pneumocystis carinii in bronchoalveolar lavage specimens taken from symptomatic HIV seropositive patients with suspected P carinii pneumonia (PCP). METHODS: Bronchoalveolar lavage specimens were obtained from 28 symptomatic HIV seropositive patients. Specimens were examined for P carinii using immunofluorescence, and by DNA amplification with PCR to obtain results on gel electrophoresis (gel) and a more sensitive Southern hybridisation (blot) technique. Specimens positive by immunofluorescence and gel electrophoresis were serially diluted to a 10(-6) concentration and each dilution strength tested for P carinii using PCR to compare quantitatively immunofluorescence with PCR. RESULTS: Of the 28 specimens analysed, 18 were negative for P carinii by both immunofluorescence and PCR, two were positive only by the blot technique of PCR, four were equivocally positive and four unequivocally positive by immunofluorescence. Three of the four equivocally positive patients tested by immunofluorescence were negative for P carinii by PCR, although one was positive by PCR (blot) technique. This patient had clinically confirmed PCP. Of the four unequivocally positive patients tested by immunofluorescence, three were gel and blot positive by PCR and had PCP clinically, but one was negative by both gel and blot techniques, although the patient certainly had PCP on clinical grounds. This patient had received nine days of treatment with high dose co-trimoxazole before bronchoalveolar lavage specimens were obtained. The three specimens positive by gel and blot techniques remained gel positive down to dilutions of between 10(-4) and 10(-6). CONCLUSIONS: PCR results may become negative soon after starting treatment for PCP. Specimens should therefore be taken before, or soon after, starting treatment. PCR seems to be between 10(4) and 10(6) times more sensitive than immunofluorescence.
Images
PMCID: PMC501145  PMID: 8459034
11.  An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital 
British Journal of Cancer  2005;92(5):867-872.
Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (⩾25 mg prednisolone or ⩾4 mg dexamethasone daily) for ⩾4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis.
doi:10.1038/sj.bjc.6602412
PMCID: PMC2361905  PMID: 15726101
Pneumocystis pneumonia; chemoprophylaxis; malignancy; corticosteroid; guidelines
12.  Transmission of Pneumocystis carinii from patients to hospital staff 
Thorax  1997;52(5):422-424.
BACKGROUND: An extrahuman reservoir of human pathogenic Pneumocystis carinii remains unknown. Host to host transmission has been described in animal studies and in cluster cases among immunodeficient patients. P carinii DNA has recently been detected in air filters from inpatient and outpatient rooms in departments of infectious diseases managing patients with P carinii pneumonia (PCP), suggesting the airborne route of transmission. Exposure of staff to P carinii may occur in hospital departments treating patients with PCP. METHODS: Exposure to P carinii was detected by serological responses to human P carinii by ELISA, Western blotting, and indirect immunofluorescence in 64 hospital staff with and 79 staff without exposure to patients with PCP from Denmark and Sweden. DNA amplification of oropharyngeal washings was performed on 20 Danish staff with and 20 staff without exposure to patients with PCP. RESULTS: There was no significant difference in the frequency or level of antibodies to P carinii between staff exposed and those unexposed to patients with PCP. None of the hospital staff had detectable P carinii DNA in oropharyngeal washings. CONCLUSIONS: There is no difference in antibodies and no detectable P carinii DNA in oropharyngeal washings, which suggests that immunocompetent staff treating patients with PCP are not a potentially infectious source of P carinii for immunocompromised patients. 



PMCID: PMC1758557  PMID: 9176532
13.  Development and Evaluation of a Quantitative, Touch-Down, Real-Time PCR Assay for Diagnosing Pneumocystis carinii Pneumonia 
Journal of Clinical Microbiology  2002;40(2):490-494.
A rapid (time to completion, <4 h, including DNA extraction) and quantitative touch-down (QTD) real-time diagnostic Pneumocystis carinii PCR assay with an associated internal control was developed, using fluorescence resonance energy transfer (FRET) probes for detection. The touch-down procedure significantly increased the sensitivity of the assay compared to a non-touch-down procedure. Tenfold serial dilutions of a cloned target were used as standards for quantification. P. carinii DNA has been detected in respiratory specimens from patients with P. carinii pneumonia (PCP) and from patients without clinical evidence of PCP. The latter probably represents colonization or subclinical infection. It is logical to hypothesize that quantification might prove helpful in distinguishing between infected and colonized patients: the latter group would have lower copy numbers than PCP patients. A blinded retrospective study of 98 respiratory samples (49 lower respiratory tract specimens and 49 oral washes), from 51 patients with 24 episodes of PCP and 34 episodes of other respiratory disease, was conducted. PCR-positive samples from colonized patients contained a lower concentration of P. carinii DNA than samples from PCP patients: lower respiratory tract samples from PCP and non-PCP patients contained a median of 938 (range, 2.4 to 1,040,000) and 2.6 (range, 0.3 to 248) (P < 0.0004) copies per tube, respectively. Oral washes from PCP and non-PCP patients contained a median of 49 (range, 2.1 to 2,595) and 6.5 (range, 2.2 to 10) (P < 0.03) copies per tube, respectively. These data suggest that this QTD PCR assay can be used to determine if P. carinii is present in respiratory samples and to distinguish between colonization and infection.
doi:10.1128/JCM.40.2.490-494.2002
PMCID: PMC153364  PMID: 11825961
14.  The unmasking of Pneumocystis jiroveci pneumonia during reversal of immunosuppression: case reports and literature review 
Background
Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.
Case presentation
We aim to better define this unique clinical syndrome by reporting two cases of PCP manifesting acutely with respiratory failure during reversal of immunosuppression in non-HIV infected patients, and reviewed the relevant literature. We searched our databases for PCP cases manifesting in the context of IRD according to our predefined case definition, and reviewed the case notes retrospectively. A comprehensive search was performed using the Medline database of the National Library of Medicine for similar cases reported previously in the English literature in October 2003. A total of 28 non-HIV (excluding our present case) and 13 HIV-positive patients with PCP manifesting as immunorestitution disease (IRD) have been reported previously in the literature. During immunorestitution, a consistent rise in the median CD4 lymphocyte count (28/μL to 125/μL), with a concomitant fall in the median HIV viral load (5.5 log10 copies/ml to 3.1 log10 copies/ml) was observed in HIV-positive patients who developed PCP. A similar upsurge in peripheral lymphocyte count was observed in our patients preceding the development of PCP, as well as in other non-HIV immunosuppressed patients reported in the literature.
Conclusions
PCP manifesting as IRD may be more common than is generally appreciated. Serial monitoring of total lymphocyte or CD4 count could serve as a useful adjunct to facilitate the early diagnosis and pre-emptive treatment of this condition in a wide range of immunosuppressed hosts, especially in the presence of new pulmonary symptoms and/or radiographic abnormalities compatible with the diagnosis.
doi:10.1186/1471-2334-4-57
PMCID: PMC539247  PMID: 15588295
15.  Clinic HIV-Focused Features and Prevention of Pneumocystis Carinii Pneumonia 
OBJECTIVE
To examine the association of clinic HIV-focused features and advanced HIV care experience with Pneumocystis carinii pneumonia (PCP) prophylaxis and development of PCP as the initial AIDS diagnosis.
DESIGN
Nonconcurrent prospective study.
SETTING
New York State Medicaid Program.
PARTICIPANTS
Medicaid enrollees diagnosed with AIDS in 1990–1992.
MEASUREMENTS AND MAIN RESULTS
We collected patient clinical and health care data from Medicaid files, conducted telephone interviews of directors of 125 clinics serving as the usual source of care for study patients, and measured AIDS experience as the cumulative number of AIDS patients treated by the study clinics since 1986. Pneumocystis carinii pneumonia prophylaxis in the 6 months before AIDS diagnosis and PCP at AIDS diagnosis were the main outcome measures. Bivariate and multivariate analyses adjusted for clustering of patients within clinics. Of 1,876 HIV-infected persons, 44% had PCP prophylaxis and 38% had primary PCP. Persons on prophylaxis had 20% lower adjusted odds of developing PCP (95% confidence interval [CI] 0.64, 0.99). The adjusted odds of receiving prophylaxis rose monotonically with the number of HIV-focused features offered by the clinic, with threefold higher odds (95% CI 1.6, 5.7) for six versus two or fewer such features. Patients in clinics with three HIV-focused features had 36% lower adjusted odds of PCP than those in clinics with one or none. Neither clinic experience nor specialty had a significant association with prophylaxis or PCP.
CONCLUSIONS
PCP prevention in our study cohort appears to be more successful in clinics offering an array of HIV-focused features.
doi:10.1046/j.1525-1497.1998.00003.x
PMCID: PMC1496898  PMID: 9462490
Pneumocystis carinii pneumonia (PCP); AIDS; clinical competence; ambulatory care; case management
16.  HIV-related Pneumocystis carinii Pneumonia in Older Patients Hospitalized in the Early HAART Era 
OBJECTIVE
To determine whether older age continues to influence patterns of care and in-hospital mortality for hospitalized persons with HIV-related Pneumocustis carinii pneumonia (PCP), as determined in our prior study from the 1980s.
DESIGN
Retrospective chart review.
PATIENTS/SETTING
Patients (1,861) with HIV-related PCP at 78 hospitals in 8 cities from 1995 to 1997.
MEASUREMENTS
Medical record notation of possible HIV infection; alveolar-arterial oxygen gradient; CD4 lymphocyte count; presence or absence of wasting; timely use of anti-PCP medications; in-hospital mortality.
MAIN RESULTS
Compared to younger patients, patients ≥50 years of age were less likely to have HIV mentioned in their progress notes (70% vs 82%, P < .001), have mild or moderately severe PCP cases at admission (89% vs 96%, P < .002), receive anti-PCP medications within the first 2 days of hospitalization (86% vs 93%, P <.002), and survive hospitalization (82% vs 90%, P < .003). However, age was not a significant predicator of mortality after adjustment for severity of PCP and timeliness of therapy.
CONCLUSIONS
While inpatient PCP mortality has improved by 50% in the past decade, 2-fold age-related mortality differences persist. As in the 1980s, these differences are associated with lower rates of recognition of HIV, increased severity of illenss at admission, and delays in initiation of PCP-specific treatments among older individuals—factors suggestive of delayed recognition of HIV infection, pneumonia, and PCP, respectively. Continued vigilance for the possibility of HIV and HIV-related PCP among persons ≥50 years of age who present with new pulmonary symptoms should be encouraged.
doi:10.1046/j.1525-1497.2001.016009583.x
PMCID: PMC1495267  PMID: 11556938
HIV; Pneumocystis carinii pneumonia; age; quality of care; outcomes
17.  Pneumocystis pneumonia in South African children diagnosed by molecular methods 
BMC Research Notes  2014;7:26.
Background
Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR.
Methods
A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded.
Results
202 children [median (interquartile range, IQR) age 3.2 (2.1– 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 – 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality.
Conclusions
The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.
doi:10.1186/1756-0500-7-26
PMCID: PMC3892044  PMID: 24410938
Pneumocystis pneumonia; HIV; Children; Prophylaxis; PCR; Diagnosis; Incidence
18.  Empirical treatment without bronchoscopy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. 
Thorax  1989;44(7):559-564.
An empirical approach to treating Pneumocystis carinii pneumonia was adopted in a prospective study of 73 men with antibodies to human immunodeficiency virus 1 (HIV-1) presenting with respiratory problems. At presentation 49 patients (group 1) were thought to have a history, findings at clinical examination, chest radiograph, and arterial blood gas tensions typical of pneumocystis pneumonia, and empirical treatment was begun immediately. Twenty four patients (group 2) were thought to have features not typical of pneumocystis pneumonia. All patients were subsequently referred for bronchoscopy to determine the diagnosis. In group 1 four patients were excluded from the analysis because bronchoscopy was not possible. Of the remaining 45, 42 had pneumocystis pneumonia, which was diagnosed at bronchoscopy in 40, and on the basis of the clinical response to co-trimoxazole in two who had negative results from investigations. Of the three patients without pneumocystis pneumonia, one patient with lymphoid interstitial pneumonitis and Branhamella catarrhalis infection would have failed to respond to empirical treatment. The other two had multiple bacterial pathogens at bronchoscopy; one already had Kaposi's sarcoma and the other would have been misdiagnosed as having AIDS. In group 2 a specific diagnosis was made at bronchoscopy in 21 cases, including pneumocystis pneumonia in seven (all had atypical chest radiographs). In three cases no diagnosis was made and spontaneous recovery occurred. Adopting an empirical approach to treatment for typical pneumocystis pneumonia (group 1) led to the correct treatment in 43 of 45 cases (95%) and would have saved 44 of the 45 of bronchoscopies in this group. Adopting an empirical approach would have caused one patient to be misdiagnosed as having AIDS. Overall, 44 out of 69 bronchoscopies (64%) would have been saved; the specificity for the diagnosis of pneumocystis pneumonia was 85% and the sensitivity was 85%. Adopting an "empirical" treatment policy for typical pneumocystis pneumonia will cause a large reduction in the number of "high risk" bronchoscopies performed.
PMCID: PMC461950  PMID: 2788935
19.  Clinical characteristics of Pneumocystis pneumonia in non-HIV patients and prognostic factors including microbiological genotypes 
Background
The number of patients with non-HIV Pneumocystis pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We investigated the clinical characteristics of non-HIV PCP and its association with microbiological genotypes.
Methods
Between January 2005 and March 2010, all patients in 2 university hospitals who had been diagnosed with PCP by PCR were enrolled in this study. Retrospective chart review of patients, microbiological genotypes, and association with 30-day mortality were examined.
Results
Of the 82 adult patients investigated, 50 patients (61%) had inflammatory diseases, 17 (21%) had solid malignancies, 12 (15%) had hematological malignancies, and 6 (7%) had received transplantations. All patients received immunosuppressive agents or antitumor chemotherapeutic drugs. Plasma (1→3) β-D-glucan levels were elevated in 80% of patients, and were significantly reduced after treatment in both survivors and non-survivors. However, β-D-glucan increased in 18% of survivors and was normal in only 33% after treatment. Concomitant invasive pulmonary aspergillosis was detected in 5 patients. Fifty-six respiratory samples were stored for genotyping. A dihydropteroate synthase mutation associated with trimethoprim-sulfamethoxazole resistance was found in only 1 of the 53 patients. The most prevalent genotype of mitochondrial large-subunit rRNA was genotype 1, followed by genotype 4. The most prevalent genotype of internal transcribed spacers of the nuclear rRNA operon was Eb, followed by Eg and Bi. Thirty-day mortality was 24%, in which logistic regression analysis revealed association with serum albumin and mechanical ventilation, but no association with genotypes.
Conclusions
In non-HIV PCP, poorer general and respiratory conditions at diagnosis were independent predictors of mortality. β-D-glucan may not be useful for monitoring the response to treatment, and genotypes were not associated with mortality.
doi:10.1186/1471-2334-11-76
PMCID: PMC3073915  PMID: 21439061
20.  Alveolar permeability in HIV antibody positive patients with Pneumocystis carinii pneumonia. 
Genitourinary Medicine  1987;63(4):268-270.
Pulmonary permeability was assessed using the technique of 99mTc (technetium-99m) diethylene triamene pentacetic acid (DTPA) aerosol transfer in 10 patients who had antibodies to human immunodeficiency virus (HIV) and were non-smokers and in 20 HIV antibody positive smokers. Five patients had Pneumocystis carinii pneumonia (PCP) proved by transbronchial lung biopsy; four were non-smokers and one a smoker. Two findings emerged: patients with PCP had greater epithelial permeability than non-smokers and smokers; and the permeability curves were monophasic in smokers and non-smokers, but biphasic in patients with PCP. The biphasic curve observed is indicative of diffuse alveolar damage and might be useful to predict PCP in patients with antibodies to HIV who have normal chest radiographs. As the study was of only five patients with PCP, however, further studies are necessary to confirm this observation.
PMCID: PMC1194081  PMID: 3308684
21.  Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study 
Thorax  2003;58(7):594-597.
Background: The opportunistic fungus Pneumocystis jiroveci is a common cause of respiratory infection in immunocompromised patients. By contrast, pneumocystis pneumonia (PCP) occurs only rarely in immunocompetent individuals. Asymptomatic colonisation with P jiroveci has recently been described in patients who are either minimally immunosuppressed or who have underlying lung disorders such as bronchiectasis. We sought to determine the prevalence of asymptomatic colonisation by P jiroveci in a cohort of adult patients undergoing diagnostic bronchoscopy.
Methods: A prospective observational cohort study was performed in patients who required bronchoscopy and bronchoalveolar lavage (BAL) as part of their routine clinical assessment. All the samples underwent standard microbiological analysis and a Grocott methenamine silver stain was performed where clinically indicated to detect the presence of P jiroveci. Polymerase chain reaction for detection of P jiroveci specific DNA was also performed.
Results: Ninety three consecutive BAL fluid samples were analysed, 17 (18%) of which contained P jiroveci DNA. Of the potential predictors examined, only glucocorticoid use was significantly associated with detectable P jiroveci DNA. Eighteen patients were receiving oral glucocorticoids (equivalent to >20 mg/day prednisolone) at the time of bronchoscopy, of whom eight (44%) had detectable P jiroveci DNA. In contrast, P jiroveci was detected in only nine of 75 patients (12%) who were not receiving glucocorticoids (difference between proportions 32%, 95% CI 8 to 57; p=0.004, two tailed Fisher's exact test).
Conclusions: P jiroveci colonisation, as determined by detection of P jiroveci DNA in BAL fluid, is common in HIV negative patients with primary respiratory disorders undergoing bronchoscopy and BAL. The higher prevalence in patients receiving corticosteroids suggests that oral glucocorticoid therapy is an independent risk factor for colonisation. In contrast, underlying lung cancer or COPD did not appear to be risk factors.
doi:10.1136/thorax.58.7.594
PMCID: PMC1746733  PMID: 12832674
22.  Pneumocystis carinii pneumonia in gastric cancer patients without acquired immune deficiency syndrome: 3 cases report and literature review 
Pneumocystis carinii pneumonia (PCP) has rarely been reported in solid tumor patients. It is a well-known complication in immunosuppressed states including acquired immune deficiency syndrome and hematologic malignancy. PCP has been reported in solid tumor patients who received long-term steroid treatment due to brain or spinal cord metastases. We found 3 gastric cancer patients with PCP, who received only dexamethasone as an antiemetic during chemotherapy. The duration and cumulative dose of dexamethasone used in each patient was 384 mg/48 days, 588 mg/69 days, and 360 mg/42 days, respectively. These cases highlight that the PCP in gastric cancer patients can successfully be managed through clinical suspicion and prompt treatment. The cumulative dose and duration of dexamethasone used in these cases can be basic data for risk of PCP development in gastric cancer patients during chemotherapy.
doi:10.4174/jkss.2012.83.1.50
PMCID: PMC3392316  PMID: 22792534
Pneumocystis carinii pneumonia; Gastric cancer; Chemotherapy
23.  Survival and treatment of AIDS patients 1984-1993: experience of a smaller east London HIV centre. 
Genitourinary Medicine  1997;73(1):44-48.
OBJECTIVE: To assess changes in survival from diagnosis of AIDS for patients managed in a small East London HIV clinic and the impact of therapeutic interventions on these survival patterns. DESIGN: Prospective observational study. SETTING: Grahame Hayton Unit, Royal London Hospital. SUBJECTS: 156 AIDS patients managed between 1984 and 1993. MAIN OUTCOME MEASURE: Survival from diagnosis of AIDS. RESULTS: Median survival for those diagnosed with AIDS before 1 January 1987 was 9.4 months compared with 27.2 months after 1 January 1987 (logrank chi 2 = 10.3, p = 0.001): CD4 count at time of AIDS and treatment with zidovudine or PCP prophylaxis were significantly associated with survival from time of AIDS. Of the 156 AIDS patients, 93 had been treated with zidovudine sometime during their follow up, 60 had received primary and 50 secondary Pneumocystis carinii pneumonia (PCP) prophylaxis. After controlling for gender, sexual orientation, age at time of AIDS, CD4 count at time of AIDS, diagnosis when first presenting to the clinic (AIDS/non-AIDS) and year of AIDS diagnosis, all patients who received either zidovudine or PCP prophylaxis had significant reductions in the risk of dying compared with those who received neither PCP prophylaxis nor zidovudine: a reduction in risk of dying between 71% (95% CI 40% to 86%) and 83% (95% CI 50% to 94%) was observed depending on the combination of zidovudine and PCP prophylaxis. CONCLUSION: A debate is currently taking place about the format and value of HIV service provision with increasing numbers of HIV infected individuals managed at smaller HIV clinics. Larger clinics concentrate clinical expertise on a single site and facilitate clinical trials. Smaller well run HIV units staffed by competent health professionals not only provide clinical outcomes similar to those obtained in the larger centres, but may also allow a more informal and intimate setting for HIV infected individuals who want to be treated nearer their area of residence.
PMCID: PMC1195759  PMID: 9155555
24.  Increased Risk of Pneumocystis Jiroveci Pneumonia among Patients with Inflammatory Bowel Disease 
Inflammatory bowel diseases  2013;19(5):10.1097/MIB.0b013e3182802a9b.
Objectives
Patients with inflammatory bowel disease (IBD) may be at increased risk for pneumocystis jiroveci pneumonia (PCP). Our aims were 1) to determine the incidence and relative risk of PCP in IBD and 2) to describe medication exposures in IBD patients with PCP.
Methods
We performed a retrospective cohort study and a case series using administrative data from IMS Health Inc, LifeLink™ Health Plan Claims Database. In the cohort, IBD patients were matched to 4 individuals with no IBD claims. PCP risk was evaluated by incidence rate ratio (IRR) and adjusted Cox proportional hazards modeling. The demographics and medication histories of the 38 cases of PCP in IBD patients were extracted.
Results
The cohort included 50,932 patients with CD, 56,403 patients with UC, and 1269 with unspecified IBD; matched to 434,416 individuals without IBD. The crude incidence of PCP was higher in the IBD cohort (10.6/100,000) than in the non-IBD cohort (3.0/100,000). In adjusted analyses, PCP risk was higher in the IBD vs. non-IBD cohort (HR 2.96, 95% CI 1.75–4.29), with the greatest risk in Crohn’s disease (CD) as compared to non-IBD (HR 4.01, 95% CI 1.88–8.56). In the IBD case series of PCP cases (n=38), the median age was 49 (IQR 43–57). A total of 20 (53%) were on corticosteroids alone or in combination with other immunosuppression.
Conclusions
Although the overall incidence of PCP is low, patients with IBD are at increased risk. IBD patients with PCP are predominantly on corticosteroids alone or in combination prior to PCP diagnosis.
doi:10.1097/MIB.0b013e3182802a9b
PMCID: PMC3879785  PMID: 23478805
inflammatory bowel disease; complications; pneumocystis; pneumonia; corticosteroids; immunosuppressive drugs
25.  Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia 
The purpose of this study was to investigate dihydropteroate synthase (DHPS) mutations and their clinical context in non-HIV-infected patients with Pneumocystis pneumonia (PCP). DHPS genes in respiratory samples collected from HIV-negative patients with PCP presented between January 2008 and April 2011 were amplified by polymerase chain reaction (PCR) and sequenced. Basic clinical data from the medical records of the patients were also reviewed. The most common point mutations, which result in Thr55Ala and Pro57Ser amino acid substitutions, were not detected in the Pneumocystis jirovecii sampled from the HIV-negative patients. Two other point mutations, which result in nonsynonymous mutation, Asp90Asn and Glu98Lys, were identified in P. jirovecii from two patients. Among the patients, the levels of lactate dehydrogenase (LDH), C-reactive protein (CRP) and plasma (1–3) β-D-glucan were elevated in 75, 92.31 and 42.86% of patients, respectively. The percentage of circulating lymphocytes was significantly lower in non-survivors than in survivors [4.2%, interquartile range (IQR) 2.4–5.85 versus 10.1%, IQR 5.65–23.4; P=0.019]. The neutrophil proportion in bronchoalveolar lavage fluid (BALF) was significantly higher in non-survivors than in survivors (49.78±27.67 versus 21.33±15.03%; P=0.047). Thirteen patients had received adjunctive corticosteroids (1 mg/kg/day prednisone equivalent) and nine (69.23%) of them eventually experienced treatment failure. No common DHPS gene mutations of P. jirovecii were detected in the HIV-negative PCP patients. However, other mutations did exist, the significance of which remains to be further identified. The elevation of neutrophil counts in BALF and reduction of the number of lymphocytes in peripheral blood may be associated with poor outcome. The efficacy of adjunctive steroid therapy in HIV-negative patients with P. jirovecii infection requires further investigation.
doi:10.3892/etm.2014.2002
PMCID: PMC4218695  PMID: 25371739
Pneumocystis jirovecii; drug resistance; dihydropteroate synthase gene; mutation

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