Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO)
Abstract:Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Dis… Show more
“…Multiple factors that are not currently recognized as stand-alone risk factors probably contribute to PCP development in a composite manner are types of solid tumors, recent administration of cancer chemotherapy, chest radiation therapy, low-dose or intermittent corticosteroids and other immunosuppressive drugs, lymphocyte count, and coexisting pulmonary diseases. As stated in latest guidelines, universal prophylaxis of PCP in these patients is not recommended, given the low incidence [ 5 ]. Nevertheless, we need to establish a method for estimating the likelihood of PCP taking multiple factors into account in patients with solid tumors with newly appearing pulmonary infiltrates.…”
Section: Discussionmentioning
confidence: 99%
“…Current international guidelines recommend primary PCP prophylaxis for patients with solid tumors, when the prolonged use of a moderate-to-high corticosteroid dose (i.e., with ≥20 mg prednisone equivalents daily for ≥4 weeks) or when temozolomide with radiation therapy is adopted [ 3 – 5 ]. Nevertheless, PCP occurs without these well-known risk factors in patients treated with intensive cancer chemotherapy.…”
Background
Pneumocystis jirovecii pneumonia (PCP)-related risk factors among patients with solid tumors are not completely defined. Thus, we aimed to characterize PCP cases with underlying solid tumors, to highlight the factors contributing to its development besides the prolonged use of moderate-to-high dose corticosteroids.
Methods
We retrospectively reviewed the medical records of patients with solid tumors diagnosed with PCP between 2006 and 2018 at a cancer center in Tokyo, Japan. Demographic and clinical data were collected, which included malignancy types, total lymphocyte count, coexisting pulmonary disease, chemotherapy, radiation therapy, corticosteroid use, and PCP-attributable mortality.
Results
Twenty cases of PCP with solid tumors were documented in 151,718 patients and 788,914 patient-years. Lung cancer (n = 6, 30%) was the most common underlying tumor, followed by breast cancer (n = 3, 15%). Only six (30%) patients were taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks from the onset of PCP. Among the remaining 14 patients, seven (50%) had coexisting pulmonary diseases, 10 (71%) had received chemotherapy within 90 days prior to PCP diagnosis, seven (50%) had undergone chest radiation therapy before PCP diagnosis, seven (50%) had received only intermittent corticosteroids, and one (7%) received no corticosteroids. Mortality attributable to PCP was 40%.
Conclusions
More than half of the patients were not taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks. Multiple other factors (e.g., lymphocytopenia, radiation to chest) may have potentially contributed to PCP in patients with solid tumors in a composite manner. We need to establish a method for estimating the likelihood of PCP taking multiple factors into account in this patient population.
“…Multiple factors that are not currently recognized as stand-alone risk factors probably contribute to PCP development in a composite manner are types of solid tumors, recent administration of cancer chemotherapy, chest radiation therapy, low-dose or intermittent corticosteroids and other immunosuppressive drugs, lymphocyte count, and coexisting pulmonary diseases. As stated in latest guidelines, universal prophylaxis of PCP in these patients is not recommended, given the low incidence [ 5 ]. Nevertheless, we need to establish a method for estimating the likelihood of PCP taking multiple factors into account in patients with solid tumors with newly appearing pulmonary infiltrates.…”
Section: Discussionmentioning
confidence: 99%
“…Current international guidelines recommend primary PCP prophylaxis for patients with solid tumors, when the prolonged use of a moderate-to-high corticosteroid dose (i.e., with ≥20 mg prednisone equivalents daily for ≥4 weeks) or when temozolomide with radiation therapy is adopted [ 3 – 5 ]. Nevertheless, PCP occurs without these well-known risk factors in patients treated with intensive cancer chemotherapy.…”
Background
Pneumocystis jirovecii pneumonia (PCP)-related risk factors among patients with solid tumors are not completely defined. Thus, we aimed to characterize PCP cases with underlying solid tumors, to highlight the factors contributing to its development besides the prolonged use of moderate-to-high dose corticosteroids.
Methods
We retrospectively reviewed the medical records of patients with solid tumors diagnosed with PCP between 2006 and 2018 at a cancer center in Tokyo, Japan. Demographic and clinical data were collected, which included malignancy types, total lymphocyte count, coexisting pulmonary disease, chemotherapy, radiation therapy, corticosteroid use, and PCP-attributable mortality.
Results
Twenty cases of PCP with solid tumors were documented in 151,718 patients and 788,914 patient-years. Lung cancer (n = 6, 30%) was the most common underlying tumor, followed by breast cancer (n = 3, 15%). Only six (30%) patients were taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks from the onset of PCP. Among the remaining 14 patients, seven (50%) had coexisting pulmonary diseases, 10 (71%) had received chemotherapy within 90 days prior to PCP diagnosis, seven (50%) had undergone chest radiation therapy before PCP diagnosis, seven (50%) had received only intermittent corticosteroids, and one (7%) received no corticosteroids. Mortality attributable to PCP was 40%.
Conclusions
More than half of the patients were not taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks. Multiple other factors (e.g., lymphocytopenia, radiation to chest) may have potentially contributed to PCP in patients with solid tumors in a composite manner. We need to establish a method for estimating the likelihood of PCP taking multiple factors into account in this patient population.
“…Durch den Einsatz antibakterieller Prophylaxen kann das Risiko von Fieber und Infektionen in Neutropenie gesenkt werden, eine Verbesserung des Gesamtüberlebens wird nicht erreicht. Aktuelle Leitlinien empfehlen unter Berücksichtigung der oben genannten antibiotikaassoziierten negativen Effekte den Einsatz einer antibiotischen Prophylaxe nur nach strenger Indikationsstellung Strenge Indikationsstellung und für Hochrisikopatienten Hochrisikopatienten [ 12 ]. Üblicherweise wird Ciprofloxacin Ciprofloxacin 500 mg 2‑mal täglich eingesetzt.…”
Section: Antiinfektive Prophylaxeunclassified
“…2 ). Wenn durch Gabe Granulozyten-Kolonie-stimulierender Faktoren Granulozyten-Kolonie-stimulierende Faktoren (G-CSF) eine ausreichende Verkürzung der Neutropeniedauer erreicht werden kann, sollten diese einer antibiotischen Prophylaxe zur Risikoreduktion vorgezogen werden [ 12 , 13 ]. Zur Vermeidung einer Pneumocystis-jirovecii -Pneumonie Pneumocystis-jirovecii -Pneumonie und zur damit verbundenen Mortalitätssenkung wird für Patienten mit hohem Risiko oder spezieller Indikation eine Prophylaxe mit Cotrimoxazol Cotrimoxazol empfohlen (Tab.…”
Hämatologische und onkologische Patienten haben aufgrund der durch die Grunderkrankung bestehenden oder therapieassoziierten Immunsuppression oftmals ein deutlich erhöhtes Infektionsrisiko. Unter Berücksichtigung weltweit zunehmender antimikrobieller Resistenzen und negativer mit der Antibiotikatherapie assoziierter Effekte sollte der angemessene und leitliniengerechte Einsatz von Antiinfektiva auch in diesem Bereich gefördert werden. Die Indikation zur antibakteriellen Prophylaxe sollte streng gestellt werden. Die Infektionsdiagnostik sowie das therapeutische Management unterscheiden sich je nach Ausmaß der erwarteten Immunsuppression und nach vorliegenden patientenindividuellen Risikofaktoren.
“…Treatment-related mortality (TRM) following induction chemotherapy with cytarabine in combination with daunorubicin occurs in about 5% of AML patients while the major cause of fatal outcome is associated with BSI. [1,2] It remains difficult to estimate the pre-treatment risk of TRM which makes clinical evaluation especially in elderly AML patients even more important. [3] The rate of distinct complications (e.g., admission to intensive care unit, mechanic ventilation or dialysis) in AML patients undergoing intensive chemotherapy has been extensively reviewed in a large cohort of AML patients considering both baseline characteristics and dynamic parameters during AML treatment.…”
Background: Infectious complications reflect a major challenge in the treatment of patients with acute myeloid leukemia (AML). Both induction chemotherapy and epigenetic treatment with hypomethylating agents (HMA) are associated with severe infections while neutropenia represents a common risk factor. Here, 220 consecutive and newly diagnosed AML patients were analyzed with respect to infectious complications dependent on treatment intensity and antifungal prophylaxis applied to these patients. Patients and Methods: We retrospectively analyzed 220 patients with newly diagnosed AML at a tertiary care hospital between August 2016 and December 2020. The median age of AML patients undergoing induction chemotherapy (n=102) was 61 years (25-76 years). Patients receiving palliative AML treatment (n=118) had a median age of 75 years (53-91 years). We assessed the occurrence of infectious complication including the classification of pulmonary invasive fungal disease (IFD) according to the EORTC/MSG criteria at diagnosis and until day 100 after initiation of AML treatment. Furthermore, admission to intensive care unit (ICU) and subsequent outcome was analyzed for both groups of AML patients, respectively. Results: AML patients subsequently allocated to palliative AML treatment have a significantly higher risk of pneumonia at diagnosis compared to patients undergoing induction chemotherapy (37.3% vs. 13.7%, P <0.001) including a higher probability of atypical pneumonia (22.0% vs. 10.8%, P =0.026). Furthermore, urinary tract infections are more frequent in the palliative subgroup at the time of AML diagnosis (5.1% vs. 0%, P =0.021). Surprisingly, the incidence of pulmonary IFD is significantly lower after initiation of palliative AML treatment compared to the occurrence after induction chemotherapy (8.4% vs. 33.3%, P <0.001) despite only few patients of the palliative treatment group received Aspergillus spp. -directed antifungal prophylaxis. The overall risk for infectious complications at AML diagnosis is significantly higher for palliative AML patients at diagnosis while patients undergoing induction chemotherapy have a significantly higher risk of infections after initiation of AML treatment. In addition, there is a strong correlation between the occurrence of pneumonia including atypical pneumonia and pulmonary IFD and the ECOG performance status at diagnosis in the palliative AML patient group. Analysis of intensive care unit (ICU) treatment (e.g. in case of sepsis or pneumonia) for both subgroups reveals a positive outcome in 10 of 15 patients (66.7%) with palliative AML treatment and in 15 of 18 patients (83.3%) receiving induction chemotherapy. Importantly, the presence of infections and the ECOG performance status at diagnosis significantly correlate with the overall survival (OS) of palliative AML patients (315 days w/o infection vs. 69 days with infection, P 0.0049 and 353 days for ECOG < 1 vs. 50 days for ECOG > 2, P <0.001, respectively) in this intent-to-treat analysis. Conclusion: The risk and the pattern of infectious complications at diagnosis and after initiation of AML therapy depends on age, ECOG performance status and subsequent treatment intensity. A comprehensive diagnostic work-up for identification of pulmonary IFD is indispensable for effective treatment of pneumonia in AML patients. The presence of infectious complications at diagnosis contributes to an inferior outcome in elderly AML patients.
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