Introduction
There are several important issues about patients with immunosuppression especially patients with malignancy. One of the most important of them is the higher risk of opportunistic infections which are common among them especially in patients with hematologic malignancies, who have received intensified chemotherapeutic regimens [1, 2]. As we see in literature there are many aspects that may be questionable during routine clinical practice and some of them would change according to new findings in clinical guidelines. The major aim of prescribing prophylactic antimicrobial therapy is to reduce the infection related morbidity and mortality [3] and the overwhelming possible infections related complications which may reduce the treatment tolerability, so use of prophylactic antimicrobials were introduced from long time ago and that was widely studied [4, 5]. However these agents are not absolutely without adverse effects.
Pneumocystis jirovecii, is an atypical fungus that transmits via airborne route in respiratory droplets. This agent is in dormitory state in immunocompetent hosts, and can transmit to others within sufficiently close distance [6]. It remains asymptomatic as long as the host would be immunocompetent [7]. Once the host becomes immunocompromised, the organism becomes activated and proliferated [8].
This agent has several components in its cell wall. The main component is β-1,3-glucan [9, 10]. The first interaction is between macrophage receptor dectin-1 and β-1,3-glucan [11, 12]. This interaction leads to activation of lung macrophages and then releasing of several pro-inflammatory cytokines such as Tumor necrosis factor α (TNFα), Interleukin 8 (IL-8) [13-15]. This pro-inflammatory state results in neutrophil and other inflammatory cells recruitment, which is correlated directly to the lung inflammation, acute respiratory failure [11, 16]. Patients with malignancy or immunodeficiency who have impaired in innate immune system function, cannot clear the fungi and are predispose to Pneumocystis jirovecii pneumonia (PCP). Also TNF blockade results in lack of immune response to Pneumocystis [17]. In addition to innate immunity, lymphocytes especially CD4+ and CD8+ play a major role in host defense against pneumocystis jirovecii. TNF, IL-1 and IL-8 directly stimulate T lymphocyte recruitment and activation [18, 19].
There are several risk factors that predispose people to developing PCP. The main factor is impaired cell mediated immunity, which has the essential role in defending against fungi. When CD4 counts drop below the 200 cells/mm as in HIV patients, Pneumocystis prophylaxis warranted. Other causes of predisposition are solid organ transplant especially renal, heart and lung transplant recipients [20, 21]. In patients with hematological or oncological malignancies who receive chemotherapeutic regimens and become neutropenic, Pneumocystis infection is likely. Also in patients receiving corticosteroid more than 15-25 mg Prednisolone or more than 4 mg Dexamethasone daily for more than 4 weeks are at higher risk of developing infection [22, 23]. These amounts of corticosteroid use are seen in chemotherapeutic regimens especially in lymphoblastic leukemia or some chemotherapeutic regimens of lymphoma. Higher dose of corticosteroid (more than 60 mg daily) or concomitant use of Cyclophosphamide would have an additional risk in developing Pneumocystis infection [24]. Alemtuzumab that causes T cell depletion predisposes to Pneumocystis infection. Other chemotherapeutic regimens such as FCR (Fludarabine, Cyclophosphamide, and Rituximab), ABVD (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine), R-CHOP (Rituximab, Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) in 14 days, also input patients into higher risk of Pneumocystis infection [25-28]. The risk of developing Pneumocystis infection in oncological malignancies are much lower than in hematological ones, so routine prescription of Pneumocystis prophylaxis are not recommended. In patients with brain tumors especially who receive an alkylating agent, Temozolamide as in patients with high grade gliomas, concurrent use of radiation therapy and also corticosteroid may increase the risk of infection [29]. Finally in patients with solid tumor who receive more than 20 mg Prednisolone or equivalents for more than four weeks are at increased risk for Pneumocystis infection, so routine prophylaxis is recommended [30]. Restoration of CD4 counts with highly active antiretroviral therapy (HAART) in HIV patients or passing of nadir phase in patients receiving chemotherapy, leads to decrease the risk of developing infection [31].
In hematologic malignancies, risk of developing PCP depends strongly on the underlying disorders. Patients with AML have much lower risk of Pneumocystis infection and up to now there is no recommendation for prophylactic use of antimicrobials for Pneumocystis in these patients. Due to limited information about the PCP incidence in AML patients, this review assess data on PCP incidence and outcome in AML.