INFECTION IN CANCER PATIENTS & PREVENTION.pptx

INFECTION IN CANCER PATIENTS & PREVENTION

1. INFECTION IN CANCER PATIENTS & PREVENTION DR B.G KARIBASAPPA DR. SAMARTH .S DR.RAVI KIRAN .S

2. INTRODUCTION Infections are a common cause of death and morbidity in patients with a wide variety of neoplasms. Bloodstream infections are the major cause of life-threatening complications in febrile neutropenic patients with hematolymphoid malignancies. The prevalence of these bloodstream infections is 20-30%. The bacteria that are most frequently isolated belong to Enterobacterae and Pseudomonas species. The overall infection attributable mortality rate is 21.5%. According to Indian studies, bloodstream infections have been reported in 6-23% of all patients with cancer and febrile neutropenia. Blood culture positivity has been noted in approximately 65% of patients with acute myeloid leukemia .

3. Febrile neutropenia is an oncological emergency in patients with hematolymphoid malignancies that predisposes them to bloodstream infections.   Blood culture is an important diagnostic modality in the management of febrile neutropenia and facilitates the identification of the causative organism with the antibiotic susceptibility pattern.   During the years 1960-70, Gram-negative bacteria were most frequently isolated ( approx 63%) from patients with cancer and neutropenia who had bloodstream infections. Among them,  E. coli was the most common organism ( approx 47%), f/b P. aeruginosa (31%) and K. pneumoniae (14.5%).

4. over the past 20-30 years, the spectrum of bloodstream infections has changed and Gram-positive organisms such as coagulase-negative Staphylococci, Streptococcus species, and Staphylococcus aureus have now increased by approximately 70-81%.   while most of the studies carried out in developing countries have reported a predominance of Gram-negative bacilli in patients with cancer and febrile neutropenia.   The genes responsible for MDR in Gram-negative bacteria are extended-spectrum beta-lactamase (ESBL), carbapenemase -resistant genes (CRE), and AmpC , while in Gram-positive bacteria, the resistant genes are mecA and glycopeptide-resistant gene, which result in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), respectively .

5. In the era of cytotoxic chemotherapy, neutropenia as a result of chemotherapy was the major cause of infectious complications of cancer therapy. Increasing use of checkpoint inhibitors and chimeric antigen receptor (CAR) T cells has changed the field of oncology and led to better outcomes. Unfortunately, checkpoint inhibitors and immunomodulators are also associated with an increased risk of infections — particularly intracellular pathogens. RISK FACTORS Intrinsic Host Factors Treatment-Related Factors

6. INTRINSIC HOST FACTORS Hematological malignancies - Certain hematologic malignancies, such as hairy CL and HL , increase infection risks, notably mycobacterial disease. Multiple myeloma and CLL heighten the risk of encapsulated bacterial infections due to impaired B-cell immunity. GATA2 mutations cause immunodeficiency, leading to viral, mycobacterial, and fungal infections in MonoMac syndrome. Solid Tumors – Tumor-related erosion of normal anatomic barriers or obstruction of the respiratory, biliary, and genitourinary tracts contributes to an increased risk of infection.

7. The relief of obstruction remains the primary therapeutic maneuver certain cancers, like colon cancer, are linked to specific bacterial infections such as Streptococcus gallolyticus . Breast tumors increase the risk of mastitis and abscess formation, usually by Staphylococcus aureus. Adrenal corticosteroid-producing tumors and ectopic adrenal corticotrophin hormone–secreting tumors are associated with an increased risk of bacterial and opportunistic infections. ASPLENIA – . Functional asplenia is present after splenectomy, splenic irradiation, and with chronic graft-versus-host disease (GVHD) The most common pathogen is Streptococcus pneumoniae, but other pathogens include Hemophilus influenzae and Neisseria meningitidis. Pathogens associated with animals ( Capnocytophaga canimorsus ) and geographic risks (Babesia, Plasmodium) should be considered

8. Treatment-Related Factors

9. Risk factors for infection in cancer patients   Cancer predisposes patients to infections through skin breaks (e.g., squamous cell carcinoma), allowing bacterial entry and leading to cellulitis. Tumor -induced obstructions (e.g., ureter or bile duct) can cause infections such as urinary tract infections or cholangitis. Normal defenses depend on the continuous emptying of organs; when blocked, bacteria can multiply and cause disease. Disruption of lymph node integrity (e.g., from radical surgeries) increases infection risk due to lymphedema and inadequate lymph drainage, commonly resulting in cellulitis.

10. 4 . Preventative measures for cellulitis include managing fluid accumulation and skin integrity, with antibiotic prophylaxis for persistent cases. 5 . Loss of spleen function (e.g., after splenectomy for cancers like hairy cell leukemia , CLL, CML, or Hodgkin's disease) impairs the reticuloendothelial system, increasing the risk of fatal infections. Patients without a spleen are highly susceptible to infections from encapsulated bacteria .

11. Infection risk depends on cancer type; e.g., multiple myeloma and CLL suggest possible hypogammaglobulinemia, often managed with prophylactic antibiotics. ALL, non-Hodgkin’s lymphoma, and patients on glucocorticoids should receive antibiotic prophylaxis against *Pneumocystis* during chemotherapy. Cancer patients may present infections atypically, such as fever in neutropenic patients, or without traditional signs like purulence or pneumonia symptoms. Patients on glucocorticoids or T-cell suppressing agents may have serious infections without fever. Cancer patients, similar to organ transplant recipients, should be closely monitored for reactivation of latent diseases like tuberculosis, herpes simplex, or zoster.

12. NEUTROPENIA – PRINCIPAL HOST DEFENCE DEFECT Definition : Neutropenia is defined as an absolute neutrophil count (ANC) of <500/ cumm or ANC that will decrease to <500 cumm in nexr 48 hrs. CIN Complication : Chemotherapy-induced neutropenia (CIN) is common and potentially fatal in myelosuppressive chemotherapy. Neutropenia is a major risk factor for infections in cancer patients. Lack of granulocytes facilitates bacterial and fungal infections, and blunts the inflammatory response, allowing infections to progress much faster. Risk Factors : CIN is linked to older age, poor nutrition, comorbidities, cancer type, prior chemotherapy, and treatment regimens.

13. Risk Assessment Tools : Tools like MASCC and CISNE help stratify FN risks but have limitations. Multinational Association for Supportive Care in Cancer   ( MASCC ) Risk Index can be used to identify low- risk patients (score ≥ 21 points), High risk – score <21 suggests serious complication including ICU Admission, hypotension, death. Clinical Index of Stable Febrile Neutropenia   (CISNE) score is a tool used to identify patients with febrile neutropenia (FN) The CISNE score has three risk levels: CISNE I: Low risk, with a score of 0 CISNE II: Intermediate risk, with a score of 1 or 2 CISNE III: High risk, with a score of 3 or higher

14. IMMUNE AUGMENTATION FOR NEUTROPENIA COLONY STIMULATING FACTORS – G-CSF, GM-CSF Both reduces time period of neutropenia Granulocyte transfusion PERSISTENT FEVER AFTER RESOLUTION OF NEUTROPENIA DRUG FEVER ( BETA LACTAM ANTIBIOTICS & RECOMB GROWTH FACTORS) TRANSFUSION REACTIONS DEEP VEIN THROMBOSIS

15. SYSTEM-SPECIFIC SYNDROMES ■ SKIN-SPECIFIC SYNDROMES Skin lesions in cancer patients : Common and may indicate systemic bacterial or fungal infections. Cellulitis : Often caused by Streptococcus or Staphylococcus , but neutropenic patients can develop infections with unusual organisms. Ecthyma gangrenosum : A necrotic skin lesion linked to Pseudomonas aeruginosa bacteremia , appearing as painless, round, black eschars with erythema. Candidemia : Associated with maculopapular rashes; diagnosis often requires punch biopsy. Neutropenic cellulitis : Spreads rapidly and lacks purulence; tiny breaks in skin can lead to severe infections.

16. Sweet syndrome : Febrile neutrophilic dermatosis, often associated with AML, characterized by the presence of leukocytes in the lower dermis,with edema of the papillary body, presents as red or bluish-red papules and nodules , Treated with high-dose glucocorticoids. Erythema multiforme : Often associated with HSV infection, while Stevens-Johnson syndrome is drug-related. Both are common in cancer patients. Cytokine-induced rashes : Occur in cancer treatments and are common in bone marrow transplant patients, who may also suffer from graft-versus-host disease. Cancer patients' immunosuppression and drug treatments make them vulnerable to infections, Drug reaction, Stevens-Johnson syndrome, and other dermatological complications.

17. ■■ GASTROINTESTINAL TRACT – SPECIFIC SYNDROMES Oral Infections : Chemotherapy can lead to mouth ulcerations, The antimetabolic effects of chemotherapy cause a breakdown of mucosal host defenses , leading to ulceration of the mouth and the potential for invasion by resident bacteria predisposing cancer patients to Viridans streptococcal bacteremia and common Candida infections. Noma : Necrotizing oral disease known as  cancrum oris , is a necrotizing ulcerative stomatitis that destroys soft tissues and bones in the mouth. including necrotizing gingitivits in immunocompromised patients, involving Bacteroides and Fusobacterium , linked to poor oral hygiene and immunosuppression. Viral Infections : HSV causes severe mucositis; acyclovir is valuable for prophylaxis and treatment.

18. Esophageal Infections : Herpes simplex and candidiasis are treatable causes of esophagitis.   Hepatic Candidiasis : Common in neutropenic patients, often presenting of persistent fever unresponsive to antibiotics, abdominal pain and tenderness or nausea, and elevated serum levels of alkaline phosphatase in a patient with hematologic malignancy who has recently recovered from neutropenia; treatment targets Candida .   Typhlitis : referred to as necrotizing colitis, neutropenic colitis , necrotizing enteropathy, characterized by Fever and right-lower-quadrant tenderness in neutropenic patients post-chemotherapy. Commonly seen with AML or ALL than among those with other types of cancer. Diagnosed through CT/MRI, treated medically; surgery is rare.   C. difficile Diarrhea : Cancer patients, susceptible to C. difficile from chemotherapy and/or antibiotics, require careful diagnosis and treatment.

19. ■ CENTRAL NERVOUS SYSTEM – SPECIFIC SYNDROMES MENINGITIS : Common in patients with lymphoma, CLL, or on chemotherapy (especially glucocorticoids). Suspected pathogens include Cryptococcus , Listeria , and encapsulated bacteria ( S. pneumoniae , H. influenzae , N. meningitidis ), especially in splenectomized and antibody-deficient patients. Other suspected bacteria include CONS, S.AUREUS,ENTEROBACTERIAE TUBERCULOSIS : Consider CNS tuberculosis in cancer patients from tuberculosis-prevalent countries.

20. Encephalitis : Expanded spectrum in immunocompromised cancer patients. Linked to intracellular organisms similar to AIDS, including Varicella-zoster virus (VZV), which can cause VZV-related vasculitis and encephalitis. Chronic viral infections may lead to dementia or progressive multifocal leukoencephalopathy (PML), especially in those treated with rituximab. Brain Masses : Present with headache, fever, or neurological issues. Infections causing brain masses may include Nocardia , fungi ( Cryptococcus , Aspergillus ), or parasites ( Toxoplasma ). Epstein-Barr virus (EBV)-associated lymphoma may also manifest as mass lesions. Biopsy may be needed for diagnosis.

21. TOXOPLASMOSIS is suspected in defective T cell immunity

22. ■ PULMONARY INFECTIONS Bacterial pneumonia in neutropenic patients may present without purulent sputum — or, in fact, without any sputum at all — and may not produce physical findings suggestive of chest consolidation. Bacterial Pneumonia in Neutropenic Patients : Diagnosis is challenging due to the lack of typical symptoms like sputum production and physical signs (e.g., rales, egophony). High-resolution CT is recommended over chest X-rays to identify infections. microscopic and microbiologic evaluation of the fluid obtained by endoscopic bronchial lavage is often diagnostic. Lavage fluid should be cultured for Mycoplasma , Chlamydia , Legionella , Nocardia , more common bacterial pathogens, fungi, and viruses.

23. the possibility of Pneumocystis pneumonia should be considered, especially in patients with ALL or lymphoma   Aspergillus Infections : Common in neutropenic patients, presenting with pleuritic chest pain, fever, and hemoptysis . CT may reveal a halo or crescent sign indicating invasive disease. Invasive Aspergillus can also cause sinus and catheter infections. Diffuse Infiltrates : Suggest viral, parasitic, or Pneumocystis pneumonia. Empirical treatment includes TMP-SMX for Pneumocystis and quinolones or azithromycin for Chlamydia , Mycoplasma , and Legionella . The presence of an elevated level of β -d-glucan in the serum of a patient being treated for cancer who is not receiving prophylaxis against Pneumocystis suggests the diagnosis of Pneumocystis pneumonia.   Chemotherapy-Induced Lung Disease : Drugs like bleomycin and alkylating agents (such as cyclophosphamide, chlorambucil, and melphalan), nitrosoureas ( carmustine [BCNU], lomustine [CCNU], and methyl-CCNU), busulfan,procarbazine , methotrexate, and hydroxyurea can cause pneumonitis, complicating diagnosis. Steroids may help with radiation-induced or drug-induced pneumonitis.

24. ■ CARDIOVASCULAR INFECTIONS Patients with Hodgkin ’ s disease are prone to persistent infections by Salmonella , sometimes (and particularly often in elderly patients) affecting a vascular site. The use of IV catheters deliberately lodged in the right atrium is associated with a high incidence of bacterial endocarditis, presumably related to valve damage followed by bacteremia . Nonbacterial Thrombotic Endocarditis (Marantic Endocarditis) : Often associated with solid tumors and sometimes following bone marrow transplantation, this condition presents with embolic events and new heart murmurs but has negative blood cultures. Infective Endocarditis and Cancer : Endocarditis may develop as a complication of cancer treatment, particularly due to catheter use, or it can be the initial manifestation of cancer, especially from gastrointestinal or genitourinary sources.

25. Infections of the Endocrine System Candida Infection of the Thyroid : Occurs in patients during the neutropenic period (low neutrophil count).. Diagnosed via indium- labeled WBC scans or gallium scans, typically after neutrophil recovery. CMV (Cytomegalovirus) Infection : Can lead to adrenalitis (inflammation of the adrenal glands),May or may not cause adrenal insufficiency (impaired adrenal function). Clinical Significance : Sudden onset of endocrine abnormalities in immunocompromised patients should raise suspicion of an underlying infection.

26. Infection Due to Vascular Compromise : Can occur when tumors restrict blood supply to muscles, bones, or joints, potentially leading to gangrene. Diagnosis Challenges : In granulocytopenic patients , physical findings may be absent. Clinicians should be proactive in obtaining tissue samples rather than relying on physical signs. Therapeutic Approach : Aggressive debridement of infected tissue may be necessary. Chemotherapy patients pose challenges due to low platelets (bleeding risk) and low WBCs (risk of secondary infections). Clostridium perfringens : Commonly associated with gas gangrene. Positive blood culture could indicate spontaneous infection from gastrointestinal lesions. Clostridium septicum Bacteremia : Linked to underlying colorectal and hematologic cancers. Musculoskeletal Infections

27. Urinary Tract Infections (UTIs) : Common in patients with compromised ureteral excretion. Candida Infections : Favors the kidney, invading either via bloodstream or retrograde through the ureters or bladder. Presence of "fungus balls" or persistent candiduria suggests invasive renal infection. Persistent Funguria : Seen with Aspergillus and Candida. Should prompt investigation for a focus of infection in the kidney. Viral Infections : BK virus (polyomavirus hominis 1) and adenovirus are often seen in immunosuppressed patients. Both viruses may be associated with hemorrhagic cystitis, especially in bone marrow transplant recipients . Renal and Ureteral Infections

28. Catheter site infections Because intravenous (IV) catheters are commonly used in cancer chemotherapy and are prone to cause infection, they pose a major problem in the care of patients with cancer. Catheter Removal : Required if red streaks appear over the subcutaneous tunnel; failure to do so may cause cellulitis and tissue necrosis. is grounds for immediate device removal. Exit-Site Infections : Common, often treated with vancomycin for coagulase-negative Staphylococcus ; catheter removal is advised for coagulase-positive Staphylococcus infections. P . aeruginosa & Candida Infections : Catheters should be removed due to difficulty in treatment and high risk of deadly bloodstream infections. Other Difficult Infections : Removal recommended for infections with Burkholderia , Stenotrophomonas , Agrobacterium , Acinetobacter , Pseudomonas , carbapenem-resistant Enterobacteriaceae, and Mycobacterium species. TUNNELED CATHETER

29. DIAGNOSTIC EVALUATION AND ANAGEMENT

30. Antibacterial Therapy & Prevention in Febrile Neutropenic Cancer Patients : Risk and Considerations : Infection risk correlates with the degree of neutropenia caused by disease or therapy. Each neutropenic patient with fever should be treated individually, with attention to prior infections and antibiotic use. Initial Treatment Guidelines : Initially Use antibiotics effective against both gram-positive and gram-negative bacteria. Monotherapy with aminoglycosides or antibiotics ineffective against gram-positives (e.g., ciprofloxacin, aztreonam) is insufficient. Fever in patients previously on antibiotics requires therapy targeting resistant pathogens . Low-risk, afebrile outpatients can be treated with oral antibiotics if neutropenia is expected to last <10 days .

31. If the pattern of resistance justifies its use, a single third generation cephalosporin constitutes an appropriate initial regimen in many hospitals. Several large-scale studies indicate that prophylaxis with a fluoroquinolone (ciprofloxacin or levofloxacin) decreases morbidity and mortality rates among afebrile patients who are anticipated to have neutropenia of long duration. Commonly used antibiotic regimens for the treatment of febrile patients in whom prolonged neutropenia (>7 days) is anticipated include (1) ceftazidime or cefepime, (2) piperacillin/tazobactam, or (3) imipenem/ cilastatin or meropenem. Vancomycin Use : Initial use of vancomycin is not routinely recommended unless there is a specific indication (e.g., catheter site infection or MRSA).

32. Culture-Based Adjustments : Adjust therapy based on blood culture results, not surface cultures. Broad-spectrum antibiotic treatment should not be stopped abruptly without evidence of infection resolution. Once treatment with broad-spectrum antibiotics has begun, it is not desirable to discontinue all antibiotics because of the risk of failing to treat a potentially fatal bacterial infection

33. Antiviral Therapy and prevention in Cancer Patients: Herpes-Group Viruses : Serious and sometimes fatal infections due to HSV and VZV are common in cancer patients receiving chemotherapy. HSV reactivation occurs in 70-80% of seropositive patients undergoing chemotherapy for leukemia or HSCT conditioning. Antiviral prophylaxis with acyclovir, valacyclovir, or famciclovir is advised for: Acute leukemia patients Seropositive HSCT recipients Myeloma patients receiving bortezomib or lenalidomide Alemtuzumab recipients (prophylaxis lasts 2 months post-therapy or until CD4 ≥200/ mcL )

34. CMV infection are more common in hematopoietic stem cell transplant recipients. CMV is significant for allo -HSCT recipients, with preemptive treatment recommended over universal prophylaxis. Prophylaxis with ganciclovir suppresses CMV but increases the risk of neutropenia and opportunistic infections. Preemptive therapy, triggered by CMV antigenemia or positive PCR results, uses antivirals such as ganciclovir, foscarnet, or valganciclovir, though each has potential toxicities. EBV lymphoproliferative disease (LPD) can occur in patients receiving chemotherapy but is much more common among transplant recipients

35. Prevention of Viral Hepatitis: Hepatitis B: HBV carriers face a risk of hepatitis flare during immunosuppressive therapy, particularly with rituximab and corticosteroids. Screening for HBsAg and anti- HBcAb is required before chemotherapy. HBV-positive patients should receive lamivudine or another antiviral during and up to 12 months post-chemotherapy. Hepatitis C: Chronic infection is common, with worsening inflammation observed during cancer therapy, especially in hematologic malignancy patients.   Hepatitis E: Chronic infection can occur in transplant patients. No specific antiviral therapy exists, but it should be considered if hepatic inflammation worsens during chemotherapy.    Respiratory Viruses :Respiratory viruses like RSV can cause severe disease in cancer patients , Influenza vaccination is recommended but may be less effective in immunocompromised individuals.

36. ANTIFUNGAL THERAPY Fungal infections in cancer patients are most often associated with neutropenia   Neutropenic patients are predisposed to the development of invasive fungal infections, most commonly those due to Candida and Aspergillus species and occasionally those caused by Mucor, Rhizopus, Fusarium.   For decades, it has been common clinical practice to add amphotericin B to antibacterial regimens if a neutropenic patient remains febrile despite 4 – 7 days of treatment with antibacterial agents.  

37. infections caused by azole-resistant Candida strains as well as aspergillosis and have been shown to be equivalent to liposomal amphotericin B for the empirical treatment of patients with prolonged fever and neutropenia. The broad-spectrum azoles (e.g., voriconazole and posaconazole) provide another option for the treatment of Aspergillus infections ,including CNS infection. Posaconazole, which is administered orally, is useful as a prophylactic agent in patients with prolonged neutropenia.

38. OTHER THERAPEUTIC MODALITIES A variety of cytokines, including granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor , enhance granulocyte recovery after chemotherapy and consequently shorten the period of maximal vulnerability to fatal infections. Recommended their use only when neutropenia is both severe and prolonged, and they should be used only in the appropriate setting (i.e., when stem cells are likely to be responsive) and not as an adjunct to antimicrobial agents. The cytokines themselves may have adverse effects, including fever, hypoxemia, and pleural effusions or serositis in other areas.

39. Granulocyte-colony stimulating factor (G-CSF) reduces febrile neutropenia incidence, recommended for patients at ≥20% risk or with previous episodes. It accelerates neutrophil recovery but hasn't shown mortality reductions. Its use for established infections remains experimental, with no proven benefits in trials. The rationale for granulocyte transfusions is to provide support for the neutropenic patient with a life-threatening infection by augmenting the number of circulating neutrophils until autologous myeloid regeneration occurs. Granulocyte transfusions, developed to support neutropenic patients with severe infections, lost favor due to improved antibiotics and concerns over toxicity and complications like HLA alloimmunization.

40. VACCINATION OF CANCER PATIENTS Adults patients should receive diphtheria – tetanus toxoid boosters at the indicated times as well as seasonal influenza vaccine. However, if possible, vaccination should not be undertaken concurrent with cytotoxic chemotherapy. The meningococcal and pneumococcal polysaccharide vaccines should be given to patients before splenectomy, if possible. The H. influenzae type b conjugate vaccine should be administered to all splenectomized patients In general, live virus (or live bacterial) vaccines should not be given to patients during intensive chemotherapy because of the risk of disseminated infection.

41. ■ EFFECT OF THE ENVIRONMENT Outbreaks of fatal Aspergillus infection have been associated with construction projects and materials in several hospitals.   The use of laminar-flow rooms and prophylactic antibiotics has decreased the number of infectious episodes in severely neutropenic patients.   Hand washing by all staff caring for neutropenic patients should be required to prevent the spread of resistant organisms.The presence of large numbers of bacteria (particularly P. aeruginosa) in certain foods, especially fresh vegetables, has led some authorities to recommend a special “ low-bacteria ” diet.

42. ■ IMMUNOGLOBULIN REPLACEMENT Many patients with multiple myeloma or CLL have immunoglobulin deficiencies as a result of their disease, and all allogeneic bone marrow transplant recipients are hypogamma globulinemic for a period after transplantation.   current recommendations reserve intravenous immunoglobulin replacement therapy for patients with severe, prolonged hypogammaglobulinemia (<400 mg of total IgG/dL) and a history of repeated infections.   Antibiotic prophylaxis has been shown to be cheaper and is efficacious in preventing infections in most CLL patients with hypogammaglobulinemia. Routine use of immunoglobulin replacement is not recommended.

43. REFERENCES - HARRISON’S PRINCIPAL OF INTERNAL MEDICINE PRINCIPLE & PRACTICE OF ONCOLOGY by DeviTa,Hellman Bajpai, V., Kumar, A., Mandal, T., Batra, A., Sarode , R., Bharti, S., Mishra, A., Sure, R., & Mishra, B. K. (2023). Prevalence of multidrug resistant bloodstream infections in febrile neutropenic patients with hematolymphoid malignancies: A retrospective observational study from a newly established tertiary oncology center in India.  Cancer Research, Statistics, and Treatment ,  6 (1), 5–12. https://doi.org/10.4103/crst.crst_266_22

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