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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.

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.

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.

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.

Extrapulmonary pneumocystosis is an exceedingly rare complication of Pneumocystis carinii pneumonia (PCP). Prior to the advent of the human immunodeficiency virus type 1 (HIV-1) epidemic, only 16 cases of extrapulmonary pneumocystosis in individuals who were immunocompromised by a variety of underlying diseases had been reported. Since the beginning of the HIV-1 and related PCP epidemic, at least 90 cases of extrapulmonary pneumocystosis have been reported. This review briefly presents a history of the discovery of P. carinii and its recognition as a human pathogen, the controversy regarding its taxonomy, and the epidemiology of this organism. A more detailed analysis of the incidence of extrapulmonary pneumocystosis in HIV-1-infected individuals and its occurrence despite widespread prophylaxis for PCP with either aerosolized pentamidine or systemic dapsone-trimethoprim is presented. The clinical features of published cases of extrapulmonary pneumocystosis in non-HIV-1-infected individuals are summarized and contrasted with those in HIV-1 infected individuals. The diagnosis of extrapulmonary pneumocystosis is discussed, and because clinical microbiologists and pathologists are the key individuals in establishing the diagnosis, the characteristic microscopic morphology of P. carinii as its appears when stained with a variety of stains is presented and reviewed. The review concludes with a brief discussion of treatments for extrapulmonary pneumocystosis.

BACKGROUND—Pneumocystis carinii is an important pathogen in immunodeficiency but may be an unrecognised cause of respiratory compromise.
OBJECTIVES—To ascertain the incidence of P carinii pneumonia (PCP) at presentation of severe combined immunodeficiency (SCID), whether it had been diagnosed, and the effect of treatment on outcome.
SETTING—The supraregional paediatric bone marrow transplant unit for primary immunodeficiencies at Newcastle General Hospital.
METHODS—Retrospective case note review of infants referred with a diagnosis of SCID from 1992 to 1998.
RESULTS—Ten of 50 infants had PCP at presentation; only one was diagnosed before transfer. Eight were diagnosed by bronchoalveolar lavage and two by lung biopsy. In only one was P carinii identified in nasopharyngeal secretions. Five required ventilation for respiratory failure but all were successfully treated with co-trimoxazole and methylprednisolone with or without nebulised budesonide. Nine survived to bone marrow transplantation and four are long term survivors after bone marrow transplantation; no deaths were related to PCP.
CONCLUSIONS—PCP is a common presenting feature of SCID but is rarely recognised. Bronchoalveolar lavage or lung biopsy are needed for diagnosis. Treatment with co-trimoxazole is highly successful.



OBJECTIVE

Although hospitalization patterns have been studied, little is known about hospital readmission among HIV-infected patients in the era of highly active antiretroviral therapy. We explored the risk factors for early readmission to a tertiary care inner-city hospital among HIV-infected patients with pneumonia in Vancouver, Canada.

DESIGN

Case-control study.

SETTING

Tertiary care, university-affiliated, inner-city hospital.

PARTICIPANTS

All HIV-infected patients who were hospitalized with Pneumocystis carinii pneumonia (PCP) or bacterial pneumonia (BP) between January 1997 and December 2000. Case patients included those who had early readmissions, defined as being readmitted within 2 weeks of discharge (N = 131). Control patients were randomly selected HIV-infected patients admitted during the study period who were not readmitted within 2 weeks of discharge (N = 131), matched to the cases by proportion of PCP to BP.

MEASUREMENTS

Sociodemographic, HIV risk category, and clinical data were compared using χ2 test for categorical variables, and the Wilcoxon rank-sum test was used for continuous variables. Multivariable logistic regression was performed to determine the factors independently associated with early readmission. We also reviewed the medical records of 132 patients admitted to the HIV/AIDS ward during the study period and collected more detailed clinical data for a subanalysis.

MAIN RESULTS

Patients were at significantly increased odds of early readmission if they left the hospital against medical advice (AMA) (adjusted odds ratio [OR], 4.26; 95% confidence interval [95% CI], 2.13 to 8.55), lived in the poorest urban neighborhood (OR, 2.03; 95% CI, 1.09 to 3.77), were hospitalized in summer season (May though October, OR, 2.36; 95% CI, 1.36 to 4.10), or had been admitted in the preceding 6 months (OR, 2.55; 95% CI, 1.46 to 4.47). Gender, age, history of AIDS-defining illness, and injection drug use status were not significantly associated with early readmission.

CONCLUSIONS

Predictors of early readmission of HIV-infected patients with pneumonia included: leaving hospital AMA, living in the poorest urban neighborhood, being hospitalized in the preceding 6 months and during the summer months. Interventions involving social work may address some of the underlying reasons why these patients leave hospital AMA and should be further studied.

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. 




Background

Patients with solid malignant tumours are at increased risk of Pneumocystis jiroveci infection from immunosuppression as a result of chemotherapy and/or radiotherapy, but active Pneumocystis pneumonia (PCP) in untreated lung cancer is uncommon.

Case presentation

A 43-year-old woman presented with prolonged fever, progressive dyspnoea, diffuse alveolar and interstitial infiltrates. Malignant cells were found on sputum cytology, confirming the diagnosis of lung cancer. She had been treated with corticosteroids and antibiotics but did not receive chemotherapy or radiotherapy. Pneumocystis jiroveci was later found in the sputum but she proved to be HIV negative.

Conclusion

Unsuspected PCP can occur in chemotherapy and radiotherapy-naïve, HIV-seronegative patients with lung cancer. The complex clinicoradiological manifestations of PCP with underlying lung cancer can lead to delay in diagnosis and may worsen the prognosis.

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.

Three HIV positive subjects presented with symptoms and radiographic changes suggestive of Pneumocystis carinii pneumonia. Methenamine silver staining of bronchoscopic alveolar lavage (BAL) fluid was negative (from one sample in one patient and two samples in the other two patients). Open lung biopsy was performed because of uncertain clinical progress and diagnosis; all three patients were found to have multiple pulmonary granulomata encasing numerous P carinii organisms. DNA amplification, using P carinii specific oligonucleotides, was performed on stored bronchoscopic BAL samples. P carinii specific amplification product was detected by ethidium bromide staining after electrophoretic separation on agarose gel in one case, and by the more sensitive technique of oligohybridisation in all three cases. In granulomatous P carinii pneumonia organisms are rarely identified in bronchoscopic alveolar lavage samples using histochemical staining, but are detectable by DNA amplification, although not at levels which can be readily distinguished from low, subclinical infection.

We report the case of a 21-year-old man who was noted to have pneumomediastinum during an admission for an acute flare of ulcerative colitis. At that time, he was on maintenance treatment with azathioprine at a dose of 1.25 mg/kg per day, and had not received supplementary steroids for 9 mo. He had never received anti-tumor necrosis factor (TNF)α therapy. Shortly after apparently effective treatment with intravenous steroids and an increased dose of azathioprine, he developed worsening colitic and new respiratory symptoms, and was diagnosed with Pneumocystis jiroveci (carinii) pneumonia (PCP). Pneumomediastinum is rare in immunocompetent hosts, but is a recognized complication of PCP in human immunodeficiency virus (HIV) patients, although our patient’s HIV test was negative. Treatment of PCP with co-trimoxazole resulted in resolution of both respiratory and gastrointestinal symptoms, without the need to increase the steroid dose. There is increasing vigilance for opportunistic infections in patients with inflammatory bowel disease following the advent of anti-TNFα therapy. This case emphasizes the importance of considering the possibility of such infections in all patients with inflammatory bowel disease, irrespective of the immunosuppressants they receive, and highlights the potential of steroid-responsive opportunistic infections to mimic worsening colitic symptoms in patients with ulcerative colitis.

In a series of 25 patients with suspected pneumonia related to the acquired immune deficiency syndrome (AIDS) the first 12 underwent routine fibreoptic bronchoscopy and bronchoalveolar lavage with or without transbronchial biopsy before treatment. Eight were found to have Pneumocystis carinii pneumonia and had typical clinical presentations with a prolonged history of symptoms, including a dry cough, and bilateral diffuse alveolar or interstitial shadowing in chest radiographs. Among the subsequent 13 cases, 11 had similar clinical presentations and were treated with high doses of intravenous co-trimoxazole without bronchoscopy first. Bronchoscopy was performed in those who deteriorated at any stage or failed to improve by the fifth day of treatment. Nine patients recovered and were discharged. In two patients who died P carinii pneumonia was confirmed in one but no diagnosis was made in the other. The early and late survival in both groups of patients was similar. In patients at high risk for AIDS who have clinical features suggestive of P carinii pneumonia starting treatment with intravenous co-trimoxazole is justified. The few patients who deteriorate or fail to respond should undergo bronchoscopy with bronchoalveolar lavage and transbronchial biopsy.

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 infection (n = 4) or malignant lymphoma (n = 2). This frequency was almost the same as those reported in Denmark and the United States. None of the six patients whose isolates had DHPS mutations were recently exposed to sulfa drugs before they developed the current episode of PCP, suggesting that DHPS mutations not only are selected by the pressure of sulfa agents but may be incidentally acquired. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n = 4 [100%] versus n = 2 [11.1%]; P = 0.002). Our results thus suggest that DHPS mutations may contribute to failures of co-trimoxazole treatment for PCP.

Forty eight patients with the acquired immunedeficiency syndrome (AIDS) presented to the Mount Sinai Hospital in New York with persistent cough and dyspnoea or an abnormal chest radiograph, or both. Thirty two (67%) were found to have Pneumocystis carinii pneumonia, either alone or in combination with another pathogen. Of these patients, eight (25%) had a normal chest radiograph. Abnormalities in the single breath carbon monoxide diffusing capacity and alveolar-arterial oxygen gradient [A-a) DO2) suggested infection with Pneumocystis carinii. Fibreoptic bronchoscopy with transbronchial biopsy was 100% sensitive in the diagnosis of pneumocytis pneumonia. Fibreoptic bronchoscopy should be undertaken in patients suspected of having a pulmonary complication of AIDS, even if the chest radiograph is normal.

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.

In recent years, clusters of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) among immunocompromised individuals have been reported. Mostly, the source of infections was suspected to be within the clinical settings when transplant recipients and PCP patients shared hospital facilities. We report on a cluster of 16 renal transplant recipients positive for P. jirovecii. None of them received anti-Pneumocystis prophylaxis prior to P. jirovecii detection. Epidemiological studies revealed that 15 of them had received kidney transplants at a German university hospital and attended the same inpatient and outpatient clinic from January through September 2006. Multilocus sequence typing (MLST) was performed on the following genes: ITS1, β-tub, 26S, and mt26S. P. jirovecii DNA was available from 14 patients and showed identical MLST types among these renal transplant recipients. Surprisingly, one patient who was treated at a different nephrological center and reported no personal contact with patients from the renal transplantation cluster harbored an identical P. jirovecii MLST type. Three HIV-positive patients and one bone-marrow-transplanted hematologic malignancy patient—treated at different medical centers—were used as controls, and different MLST types were revealed. Interestingly, in three of the four previously described regions, new alleles were detected, and one new polymorphism was observed in the mt26S region. The epidemiological data and the genotyping results strongly suggest a nosocomial patient-to-patient transmission of P. jirovecii as the predominant transmission route. Therefore, strict segregation and isolation of P. jirovecii-positive/suspected patients in clinical settings seems warranted.

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.

Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) alone was found to be as effective as low-dose TMP-SMX plus zidovudine and standard-dose TMP-SMX alone in preventing and treating Pneumocystis carinii pneumonia (PCP) in an immunosuppressed-rat model. Zidovudine alone had no preventive or curative effect on PCP. We conclude that the initially reported reduced incidence of PCP in human immunodeficiency virus-infected patients treated with zidovudine alone is not due to anti-P. carinii activity of zidovudine. Furthermore, the clinical efficacy of low-dose TMP-SMX for the prevention and treatment of PCP should be further investigated.

Aim—To compare the techniques and results of a nested PCR and an immunofluorescence assay (IFA) for the detection of Pneumocystis carinii infection; to consider the role of the nested PCR in the diagnosis of P carinii pneumonia (PCP).

Methods—Serial dilutions of two known P carinii positive samples were tested by IFA and PCR to determine their relative sensitivities. Seventy eight respiratory samples (15 from 11 patients with HIV infection/acquired immunodeficiency syndrome (AIDS) and 63 from 42 patients with other forms of immunodeficiency) were tested using both assays, and the costs and technical requirements of each assay were assessed.

Results—The PCR had a greater relative sensitivity over the IFA of 2 × 101 to 2 × 103 fold in a postmortem lung sample and 2 × 105 to 2 × 106 fold in a bronchoalveolar lavage sample from a patient with PCP. P carinii was detected in all 15 samples from the patients with HIV/AIDS by both IFA and PCR. Of the 63 samples from the patients with immunodeficiencies other than HIV/AIDS, the PCR was more sensitive than IFA.

Conclusions—The nested PCR is a more sensitive assay than the IFA. It may be useful in the diagnosis of PCP in patients with immunodeficiencies other than HIV/AIDS. Similarly, PCR may be of benefit for this patient group as less invasive specimens are needed. PCR has an increasing role to play in the diagnosis of PCP in the routine laboratory.

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.

We report a molecular typing and epidemiologic analysis of Pneumocystis carinii pneumonia (PCP) cases diagnosed in our geographic area from 1990 to 2000. Our analysis suggests that transmission from patients with active PCP to susceptible persons caused only a few, if any, PCP cases in our setting.

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.

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.

BACKGROUND--Despite the immune suppression, frequent hospital admissions, and many intercurrent illnesses associated with HIV infection, Pseudomonas aeruginosa has been cited relatively infrequently as a respiratory pathogen in HIV positive patients. METHODS--The microbiological isolates, medical records, radiographic reports, and laboratory data from 224 patients undergoing sputum induction and/or bronchoalveolar lavage for evaluation of respiratory symptoms suspicious for Pneumocystis carinii pneumonia (PCP) from 1989 to 1992 were reviewed retrospectively. RESULTS--An increasing number of respiratory isolates with Pseudomonas aeruginosa was found over this time period. Eighteen of the 224 patients were identified in whom P aeruginosa was recovered on at least one occasion. These patients were more likely to have a history of smoking and prior PCP than those in whom Pseudomonas was not recovered. Mean CD4 counts were also significantly lower in these patients. CONCLUSIONS--Pseudomonas aeruginosa may be recovered from a substantial number of respiratory isolates from HIV positive patients suspected of having PCP. The prevalence of this phenomenon may be increasing.