Pneumocystis carinii pneumonia is a severe form of infection and inflammation of the lungs that primarily affects immunodeficient individuals. Its causative agent pertains to the genus Pneumocystis.
Presentation
The clinical picture presented by PP patients may be dominated by symptoms associated with pneumonia, other opportunistic infections (e.g., infections with Mycobacterium spp., Cryptococcus neoformans or Toxoplasma gondii) or the underlying disease itself. PP-associated symptoms progress slowly. It is often not possible to retrospectively define a clear time of onset. The severity of symptoms related to opportunistic infections does generally correlate with the degree of lymphopenia. Of note, spontaneous pneumothorax occurs in a small share of PP patients may cause a rather acute worsening of symptoms.
Fever, non-productive cough, dyspnea and hypoxemia (PaO2 < 75 mmHg) - both of which aggravate under exercise -, and lactate dehydrogenase levels exceeding 400 U/L are generally considered good indicators of PP, but few patients present all these symptoms. However, the majority of PP patients does show at least three of them. Recently, (1-3)-β-d-glucan, Krebs von den Lungen-6 antigen, and S-adenosyl methionine (SAM) have been proposed as additional serologic biomarkers with cutoffs set at 100 pg/mL, 580 U/mL, and 50 nmol/L, respectively [9]. Such serum concentrations should be analyzed in case of mild PP and unclear clinical symptoms.
Auscultation may not yield any remarkable findings, but dry rales may be heard. Similarly, interstitial infiltrates may be visible in plain radiographs but are not an exclusion criterion.
Entire Body System
- Fever
) ornithosis ( A70 ) pneumocystosis ( B59 ) pneumonia NOS ( J18.9 ) ICD-10-CM Diagnosis Code J17 Pneumonia in diseases classified elsewhere 2016 2017 2018 2019 Billable/Specific Code Manifestation Code Code First underlying disease, such as: Q fever [icd10data.com]
Adverse effects and hypersensitivity reactions are common in such patients and include fever and maculopapular rash. [patient.info]
The second patient was a 22-year-old woman presenting with a 4-day history of malaise, cough, dyspnea, and fever. She had concomitant Mycobacterium tuberculosis infection. [ncbi.nlm.nih.gov]
- Pain
We present the case of a 64-year-old woman presenting with rapid onset, painful distal symmetrical lower limb weakness and an acute kidney injury. [ncbi.nlm.nih.gov]
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In September of the same year, he started to experience a deterioration in renal function and uraemia, accompanied by fever and pain in the area of the graft (left iliac fossa). [revistanefrologia.com]
Dry cough or wheezing Shortness of breath Fatigue Chest pain or tightness when you breathe Chills Weight loss Symptoms usually come on slowly, over several weeks, in people who have HIV. [webmd.com]
- Fatigue
Dry cough or wheezing Shortness of breath Fatigue Chest pain or tightness when you breathe Chills Weight loss Symptoms usually come on slowly, over several weeks, in people who have HIV. [webmd.com]
Disseminated infection Hypoxemia Respiratory failure Pneumothorax Death Immunosuppression, as from HIV infection, leukemia, lymphoma, or organ transplantation Dyspnea on exertion progressing to continuous dyspnea Weakness Fatigue Malaise Nonproductive [quizlet.com]
They often have pallor, weight loss, and fatigue on exertion and become short of breath even when speaking. [medical-dictionary.thefreedictionary.com]
- Hypoxemia
Differential responses to the sequential treatments for PCP and IVL implied that increased serum lactate dehydrogenase (LDH) was due to PCP, whereas hypoxemia and dementia were due to IVL. [ncbi.nlm.nih.gov]
This case emphasizes the need for clinicians to have a high index of suspicion and consider PE in the differential diagnoses of dyspnea and hypoxemia, particularly when PJP infection or other AIDS-defining illnesses are suspected. [journals.lww.com]
PJ causes a diffuse pneumonitis characterized by fever, dyspnea at rest, tachypnea, hypoxemia, nonproductive cough, and bilateral diffuse infiltrates in the roentgenogram. [unboundmedicine.com]
In addition, for the studies in patients with hypoxemia, we also focused on mortality due to severe hypoxemia (PaO 2 mmHg) in non-HIV cases of PJP. [archbronconeumol.org]
If any hypoxemia is found (O2 saturation 14. Procedures Obtain sputum sample by sputum-induction for histopathologic testing if PCP is strongly suspected. [slideshare.net]
- Asymptomatic
0.35-0.73 (range 0.1-0.8%) (asymptomatic vs control P < 0.0001). [ncbi.nlm.nih.gov]
Pregnancy and asymptomatic carriage of Pneumocystis jiroveci. Emerg Infect Dis 2003; 9:605-606 [Google Scholar] [ajronline.org]
Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy, a prospective study. Thorax 2003 ; 58 : 594 –7. Vargas SL, Ponce C, Sanchez CA, et al. Pregnancy and asymptomatic carriage of Pneumocystis jiroveci. [thorax.bmj.com]
Environmentally acquired Asymptomatic infection appears early in life; >70% of healthy individuals have antibodies by age 4 years. Primary infection is likely to be the mechanism in infants. [unboundmedicine.com]
Maskell NA, Waine DJ, Lindley A, et al: Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study. Thorax 2003;58(7):594-597 3. [mayomedicallaboratories.com]
Respiratoric
- Cough
Most patients had fever, progressive dyspnea, and dry cough at onset of PCP. The mean duration of symptoms before PCP diagnosis was 7 days. Absolute lymphocyte counts ranged from 126 to 528/microL. [ncbi.nlm.nih.gov]
Presentation [ 3, 9 ] Cough is usually non-productive but productive cough may occur in up to a third of patients. Exertional dyspnoea. Fever. Tachypnoea. Chest pain. [patient.info]
Physical examination Common symptoms include fever, dyspnea on exertion, nonproductive cough, stridor, nasal flaring, and chest tightness. If the patient has a cough, note the type. [medical-dictionary.thefreedictionary.com]
Pneumocystis Jirovecii (carinii) Pneumonia Clinical features fever cough tachypnoea (very characteristic rapid shallow breathing) absence of signs on auscultation (unless patient is fluid-overloaded) hypoxaemia lymphopenia CXR classically with diffuse [starship.org.nz]
- Dyspnea
The second patient was a 22-year-old woman presenting with a 4-day history of malaise, cough, dyspnea, and fever. She had concomitant Mycobacterium tuberculosis infection. [ncbi.nlm.nih.gov]
- Respiratory Distress
This child presented with bacterial pneumonia and respiratory distress, presumed to be c... Fig C 43-4 Pneumocystis carinii pneumonia in AIDS. [5minuteconsult.com]
A secondary E. coli infection was superimposed and the patient died of disseminated intravascular coagulation and adult respiratory distress syndrome. [ncbi.nlm.nih.gov]
- Dry Cough
Most patients had fever, progressive dyspnea, and dry cough at onset of PCP. The mean duration of symptoms before PCP diagnosis was 7 days. Absolute lymphocyte counts ranged from 126 to 528/microL. [ncbi.nlm.nih.gov]
Common symptoms of PCP include tiredness, fever, breathlessness and a dry cough. Where tests to identify Pneumocystis are unavailable, a person will often be treated for PCP based on their symptoms alone. [health24.com]
- Pleural Effusion
Pneumonia with large pleural effusion. This child presented with bacterial pneumonia and respiratory distress, presumed to be caused in part by the large pleural effusion. [5minuteconsult.com]
We report a case of a renal transplant recipient with PCP and moderate-sized pleural effusion with pneumocystis cysts. [ncbi.nlm.nih.gov]
Chest radiograph (CXR) showed bilateral reticular markings with no pleural effusions (fig. 1a ⇓ ). [erj.ersjournals.com]
Cardiovascular
- Cyanosis
Respiration becomes abdominal, the cough is unproductive, and cyanosis increases in spite of oxygen therapy. Emphysema with a few scattered râles may be the only physical finding. The hemogram is not characteristic. [pubs.rsna.org]
PNEUMONIA, Pneumocystis carinii type, or interstitial plasma cell pneumonia, is a peculiar type of infantile pneumonitis characterized by progressive dyspnea, tachypnea, tachycardia, and cyanosis.1 Although, auscultatory findings are minimal, radiograms [jamanetwork.com]
The characteristic clinical picture is one of progressive respiratory distress and cyanosis, with relatively few physical findings pertaining to the thorax. [ajronline.org]
Workup
Most PP patients present with a medical history that allows their allocation into one or more of the above mentioned risk groups. Any condition possibly related with CD4+ lymphopenia and respective cell counts <200 cells/µL are strong indicators of an opportunistic infection [10]. Thus, a thorough anamnesis and a complete hemogram need to be established in every case where clinical presentation is consistent with PP.
In order to confirm a tentative diagnosis of PP, sputum induction or bronchoalveolar lavage should be carried out to obtain samples that may be tested for the presence of Pneumocystis jirovecii. Detection of Pneumocystis spp. is realized by preparation and traditional or immunofluorescent staining of a smear; to date, fungal culture of these pathogens has not been established. However, if microscopic analysis yields negative results despite a strong suspicion for PP, molecular biological methods, namely real-time and/or reverse-transcription polymerase chain reaction, may be applied to increase the sensitivity of testing [11]. However, diagnosis should not only rely on these findings and visualization of Pneumocystis jirovecii is still the gold standard for diagnosis of PP.
In case neither of the aforementioned diagnostic approaches yields satisfying results and if findings are not consistent with any differential diagnosis, transbronchial or open lung biopsy should be performed. Meanwhile, empiric antimicrobial treatment is recommended.
Of note, confirmation of PP does not rule out the presence of pulmonary comorbidities particularly because PP patients are immunodeficient and thus highly susceptible to many infectious diseases.
X-Ray
- Pulmonary Infiltrate
We describe a 34-year-old man with human immunodeficiency virus infection who received successful treatment of minimally symptomatic Pneumocystis carinii pneumonia and who subsequently developed diffuse pulmonary infiltrates and hypoxia 2 weeks after [ncbi.nlm.nih.gov]
Transtracheal aspiration yielded material containing pneumocysts in 8 (13%) of 60 patients; each had pulmonary infiltrates and clinical courses consistent with P carinii pneumonia. [jamanetwork.com]
The roentgen findings are those of diffuse, granular pulmonary infiltrates which progress from the hili toward the periphery of the lung, becoming more and more confluent. [ajronline.org]
- Pulmonary Infiltrates
We describe a 34-year-old man with human immunodeficiency virus infection who received successful treatment of minimally symptomatic Pneumocystis carinii pneumonia and who subsequently developed diffuse pulmonary infiltrates and hypoxia 2 weeks after [ncbi.nlm.nih.gov]
Transtracheal aspiration yielded material containing pneumocysts in 8 (13%) of 60 patients; each had pulmonary infiltrates and clinical courses consistent with P carinii pneumonia. [jamanetwork.com]
The roentgen findings are those of diffuse, granular pulmonary infiltrates which progress from the hili toward the periphery of the lung, becoming more and more confluent. [ajronline.org]
- Ground Glass Appearance
Both show ground glass opacities. [en.wikipedia.org]
Another chest X-ray was requested, which showed a bilateral interstitial pattern with a ground glass appearance (Figure 1). [revistanefrologia.com]
High-resolution computed tomography reveals interlobular septal thickening and patchy areas resembling a ground-glass appearance. Gallium scan may show increased uptake over the lungs. [quizlet.com]
- Bilateral Pulmonary Infiltrates
Patients were hospitalised at mean age of 5 days (range 1-20) and their illness was characterised by its afebrile course, presentation in crisis with severe respiratory distress, bilateral pulmonary infiltrates with hyperaeration. [nature.com]
We report the case of a patient who, having recommenced haemodialysis after eight years with a functioning renal graft, developed progressive respiratory symptoms with bilateral pulmonary infiltrates, showing Pneumocistis jiroveci pneumonitis after recent [revistanefrologia.com]
- X-Ray Abnormal
Confirming the diagnosis Chest X rays characteristically demonstrate bilateral interstitial/reticular or granular opacities, but Pneumocystis pneumonia may present with a normal or minimally abnormal chest X ray in a subset of cases. [hivinsite.ucsf.edu]
Diagnostic investigations include chest X-ray, computed tomography, blood gases (PaO 2 ), sputum culture, bronchoscopy with alveolar lavage and lung biopsy. [pharmaceutical-journal.com]
Serum
- Leukopenia
The blood tests were unremarkable apart from a moderate to severe leukopenia. [ncbi.nlm.nih.gov]
Occurrence of leukopenia or neutropenia and their duration were not reported consistently. [cochrane.org]
At that time, he also had a low platelet count associated with persistent anemia and leukopenia. [scielo.br]
About 50 per cent of people treated with co-trimoxazole experience side effects. 3 These commonly include rashes, headache, nausea, diarrhoea, leukopenia and hepatic inflammation. [pharmaceutical-journal.com]
- Hypercapnia
This leads to a lack of oxygen (hypoxemia) and an increase in carbon dioxide (hypercapnia). To compensate for this, people with severe pneumonia often breathe very quickly and shallower (tachypnea). [imedicalsociety.org]
Pleura
- Pleural Effusion
Pneumonia with large pleural effusion. This child presented with bacterial pneumonia and respiratory distress, presumed to be caused in part by the large pleural effusion. [5minuteconsult.com]
We report a case of a renal transplant recipient with PCP and moderate-sized pleural effusion with pneumocystis cysts. [ncbi.nlm.nih.gov]
Chest radiograph (CXR) showed bilateral reticular markings with no pleural effusions (fig. 1a ⇓ ). [erj.ersjournals.com]
Treatment
Antimicrobial treatment is indicated in PP patients and long-term treatment regimes are required to eliminate the pathogen in case of severe immunodeficiency [12]. As has been stated above, trimethoprim-sulfamethoxazole is the drug of choice. While antibiotic resistance rarely causes therapy failure, side effects often restrict the highest applicable dosage and impede successful treatment. In fact, it has been estimated that about one third of PP therapies fails due to drug toxicity. Commonly observed side effects and adverse events are nausea, vomiting, bone marrow suppression and hepatitis. Adjunctive treatment to relieve these side effects is required in most cases of PP.
An alternative treatment option is pentamidine, but this drug mediates toxic effects on pancreas and kidneys. Similarly, trimetrexate may be applicated as second-line drug, but bone marrow suppression may become a serious problem if not treated adequately. Clindamycin plus primaquine has also been reported as an effective therapeutic approach with anemia being a common side effect.
Both trimethoprim-sulfamethoxazole as well as trimetrexate may be combined with dapsone in order to augment therapeutic efficacy without increasing the risk for specific side effects.
Corticosteroids are indicated in patients with a PaO2 < 70 mm Hg. Here, the benefits clearly outweigh possible side effects and immunosuppressive therapy has indeed been proven to increase the chance of survival.
Prognosis
If left untreated, PP is associated with a very high mortality. Death occurs due to respiratory failure and unfortunately this outcome is observed in a significant share of HIV-positive PP patients who don't have access to adequate medical care or who do not (yet) receive prophylactic treatment [8]. Early diagnosis and adequate treatment significantly improve the chance of survival, but opportunistic infections like PP are still a major cause of death in HIV-positive individuals. Similarly, prophylactic administration of antimicrobial drugs reduces the risk for PP and thus increases the likelihood of a positive outcome in patients whose immunodeficiency is not related to an HIV infection.
Etiology
As has been indicated above, the etiologic agent of PP is Pneumocystis jirovecii. This pathogen has been considered a protozoa for a long time, but is now classified as an ascomycete fungus.
While large shares of the population are exposed to Pneumocystis jirovecii at some point in their lives - most often first exposure occurs during childhood - PP only develops in severely immunocompromised patients. While this condition may result from distinct diseases, it may also be induced iatrogenically in order to treat existing comorbidities. Consequently, the following individuals are at risk for PP:
- Patients suffering from an infection with the human immunodeficiency virus (HIV). Here, very low counts of CD4+ lymphocytes and additional opportunistic infections, e.g., infection with Cryptococcus neoformans, are unfavorable prognostic factors regarding a possible development of PP.
- Those presenting with any disease that interferes with immune function, mainly patients diagnosed with primary immune deficiencies or hematological malignancies.
- Patients receiving long-term immunosuppressive medication, possibly because they required an organ transplant or because of rheumatoid arthritis [3].
- Individuals having pre-existing lung disease [4].
Epidemiology
PP has classically been associated with HIV infections and before highly active anti-retroviral therapy was available, the vast majority of HIV patients suffered from infections with this opportunistic pathogen. Prevalence could be diminished further by applying PP prophylaxis, particularly in patients who showed severe CD4+ lymphopenia. However, these epidemiological data basically apply for developed countries where many patients have access to the necessary medication. In developing countries like those ubicated in Sub-Saharan Africa, PP case numbers increase [5]. While this may be partially due to improvements in diagnostic approaches, the overall increase of HIV prevalence and poor medical care are assumed to mainly account for this trend.
Similar developments can be observed among HIV-negative PP patients. Immunomodulatory drugs are increasingly used to treat a variety of diseases and are administered in particularly high doses to patients that require organ transplants. Here, routine antimicrobial prophylaxis allowed for a reduction of PP prevalence from more than 75% to very low numbers.
PP prevalence is increasing outside the known risk groups [4].
Pathophysiology
Pneumocystis jirovecii may be isolated from samples obtained from many healthy individuals [6]. This observation is in agreement with the hypothesis that the etiologic agent of PP is transmitted by infected patients [7]. However, defense mechanisms employed by immunocompetent people do not allow for extensive reproduction of this pathogen and these individuals remain asymptomatic. To date, it is not clear whether healthy individuals are able to infect patients susceptible for PP, since the above stated theory has been deducted from hospital outbreaks that involved only immunodeficient patients.
Presumably, Pneumocystis jirovecii is transmitted by droplet infection. Pneumocystis throphozoites measures less than 5 µm in diameter and is thus able to reach pulmonary alveoli. Trophozoites may reproduce asexually or create cysts that reproduce sexually. According to current knowledge, a major cyst releases several trophozoites. Although further research is required to confirm these assumptions regarding the life cycle of Pneumocystis jirovecii, it is already known that patients with impaired cellular and humoral immunity are unable to inhibit pathogen reproduction. CD4+ lymphopenia has been identified as a major risk factor for PP and this can be explained by the fact that alveolar macrophages need to interact with the former in order to eliminate pathogens like Pneumocystis jirovecii.
Consequently, immunodeficient patients develop severe interstitial pneumonia after infection with Pneumocystis jirovecii. This condition leads to dyspnea, respiratory insufficiency, hypoxemia and respiratory alkalosis.
Prevention
Although antibiotics may be administered prophylactically, side effects usually limit their applicability. Thus, preventive measures should be adjusted to the response of every individual patient - some may tolerate a certain drug better than others and will benefit from prophylactic administration of drugs like trimethoprim-sulfamethoxazole. If at all possible, the underlying disease should be treated to improve the patient's response to the presence of Pneumocystis jirovecii while reducing the need for prophylactic application of antimicrobial compounds.
Summary
Pneumocystis carinii pneumonia is a severe form of interstitial pneumonia that primarily affects immunocompromised patients. It is triggered by an infection with fungal pathogens pertaining to the genus Pneumocystis. Until recently, Pneumocystis carinii has been assumed to be the causative agent of this disease. However, molecular biological analyses of Pneumocystis species have revealed that the human pathogen differs from Pneumocystis carinii and constitutes a separate species [1]. It has been named Pneumocystis jirovecii. Nevertheless, many practitioners still use the designation Pneumocystis carinii pneumonia, a term that is commonly abbreviated PcP. As can be deducted from the above described findings, Pneumocystis jirovecii pneumonia or PjP may be the more precise name of the disease. In order to avoid confusion to this end, this article will merely refer to Pneumocystis pneumonia (PP).
Pneumocystis jirovecii is an opportunistic pathogen that may be isolated from large shares of the healthy population in distinct parts of the world. However, immunosuppression - either due to immune disorders or immunomodulatory treatment - facilitates pathogen reproduction and may lead to severe, potentially fatal interstitial pneumonia. Commonly observed clinical symptoms of PP are fever, dyspnea and non-productive cough. Diagnostic imaging typically reveals interstitial infiltrates, but is not considered a very sensitive technique. In order to confirm a tentative diagnosis of PP, detection of the pathogen in sputum or bronchoalveolar lavage fluid is required.
Administration of high doses of trimethoprim-sulfamethoxazole is the treatment of choice. Such medication may also be used prophylactically in patients pertaining to any risk group. However, potential side effects may outweigh the benefits of therapeutic or preventive application of antimicrobial drugs and the possibility to lower doses should seriously be considered [2]. Adjunctive therapy with immunosuppressants may help to limit the inflammatory reaction but does often exacerbate the underlying disease. Thus, corticosteroids are only applied in severe cases of PP.
Mortality is still rather high and is principally associated with delayed diagnosis and initiation of treatment, secondary bacterial infection and severe underlying diseases. However, wide availability of antibiotics and few resistances in Pneumocystis strains have contributed considerably to improve the prognosis of PP patients.
Patient Information
Pneumocystis carinii pneumonia (PP) is a severe infection and inflammation of the lungs. It is caused by a fungal pathogen designated Pneumocystic jirovecii, formerly known as Pneumocystic carinii. This microorganism is an opportunistic pathogen, i.e., it does not induce any disease in otherwise healthy individuals, but does cause detrimental effects in susceptible people. Susceptibility to PP strongly correlates with immunodeficiency, which is why this disease is mainly diagnosed in patients suffering from an infection with the human immunodeficiency virus, from hematological malignancies or genetic disorders that interfere with their immune function. On the other hand, immunodeficiency may be induced by certain drugs that are prescribed to patients who received an organ transplant or who suffer from autoimmune diseases like rheumatoid arthritis.
In those patients, Pneumocystic jirovecii may induce an interstitial pneumonia. Commonly observed symptoms are fever, difficulties to breathe and non-productive cough. These symptoms aggravate under exercise and progress slowly. They may, however, significantly interfere with pulmonary function. In fact, untreated PP is associated with a very high mortality. Fortunately, mortality can be diminished significantly by means of antibiotic treatment. Trimethoprim-sulfamethoxazole is the drug of choice to treat PP patients, but some may not tolerate it and suffer side effects like nausea, vomiting, bone marrow suppression and hepatitis. In such cases, alternative treatment options have to be applied.
References
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- Creemers-Schild D, Kroon FP, Kuijper EJ, de Boer MG. Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study. Infection. 2016; 44(3):291-299.
- Bruce ES, Kearsley-Fleet L, Watson KD, Symmons DP, Hyrich KL. Risk of Pneumocystis jirovecii pneumonia in patients with rheumatoid arthritis treated with inhibitors of tumour necrosis factor alpha: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology (Oxford). 2016; 55(7):1336-1337.
- Maini R, Henderson KL, Sheridan EA, et al. Increasing Pneumocystis pneumonia, England, UK, 2000-2010. Emerg Infect Dis. 2013; 19(3):386-392.
- Murray JF. Pulmonary complications of HIV-1 infection among adults living in Sub-Saharan Africa. Int J Tuberc Lung Dis. 2005; 9(8):826-835.
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- Yazaki H, Goto N, Uchida K, Kobayashi T, Gatanaga H, Oka S. Outbreak of Pneumocystis jiroveci pneumonia in renal transplant recipients: P. jiroveci is contagious to the susceptible host. Transplantation. 2009; 88(3):380-385.
- Bonnet F, Lewden C, May T, et al. Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France. Scand J Infect Dis. 2005; 37(6-7):482-487.
- Esteves F, Cale SS, Badura R, et al. Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers. Clin Microbiol Infect. 2015; 21(4):379 e371-310.
- Avino LJ, Naylor SM, Roecker AM. A Review of Pneumocystis jirovecii Pneumonia in the Non-HIV-Infected Population. Ann Pharmacother. 2016.
- Fillaux J, Malvy S, Alvarez M, et al. Accuracy of a routine real-time PCR assay for the diagnosis of Pneumocystis jirovecii pneumonia. J Microbiol Methods. 2008; 75(2):258-261.
- Wilkin A, Feinberg J. Pneumocystis carinii pneumonia: a clinical review. Am Fam Physician. 1999; 60(6):1699-1708, 1713-1694.