Immunodeficiency diseases are clinical syndromes that occur when any part of the immune system or its components develop abnormally due to congenital underdevelopment or acquired damage caused by various factors, resulting in abnormal development, differentiation, proliferation and metabolism of immunologically active cells and causing immune insufficiency.
Immunodeficiency diseases can generally be divided into two categories: congenital or primary immunodeficiency diseases and acquired or acquired immunodeficiency diseases. With the development of organ transplantation and chemotherapy for malignancies, the number of patients with secondary immunodeficiency diseases is increasing, and infections have become the most important factor affecting the course and healing of these patients, with pulmonary infections being the most common. Lung infections in patients with immune-compromised hosts are increasingly becoming an important medical problem and are an important cause of high incidence and mortality of lung infections. Xin Jianbao, Department of Respiratory Medicine, Wuhan Union Hospital, in addition to HIV.
I. Other causes of immune compromised hosts such as.
1, infection: many viruses, bacteria, fungi, protozoa and other acute and chronic infections.
2, malignancies: such as Hodgkin’s disease, lymphosarcoma, various types of acute leukemia and chronic lymphocytic leukemia, and myeloma; or advanced tumors and severe malnutrition caused by cachexia.
3, immunosuppressants and antibiotics and other drugs: such as corticosteroids, cyclophosphamide, azathioprine, thiopurine, aminopterin, cyclosporine A, anti-T lymphocyte immunoglobulin (ATG) and gamma radiation, as well as certain antibiotics.
4, malnutrition and excessive nutrition.
5, liver and kidney insufficiency.
6, diabetes, Cushing’s syndrome, large burns, chest catheter drainage, anesthesia and larger surgical procedures, premature babies, newborns and infants less than 1 year old, and elderly people over 60 years old are all causes of immune compromised hosts.
Second, the common pathogens of immunocompromised infection
1. Bacteria: Bacterial infections can occur in any period of immune deficiency, especially when immune function is severely depressed for an extended period of time, and bacterial infections are very likely to occur. Common gram-negative pathogenic bacteria are Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli, and the gastrointestinal mucosa break is often the invasion site of gram-negative bacilli. Common gram-positive bacteria are Streptococcus haemolyticus, Staphylococcus epidermidis and Staphylococcus aureus. Of particular note are Staphylococcus aureus and Pseudomonas aeruginosa as the most common bacterial infections.
2, fungi: ICH patients with lung infections, the proportion of fungal infections reached 17%. Among them, the highest incidence of invasive Aspergillus and Candida. There are also some geographic fungal diseases, such as histoplasmosis, coccidioidomycosis, etc.
3, viruses: human cytomegalovirus, herpes simplex virus, varicella-zoster virus, adenovirus, etc. can cause infection in immunocompromised patients. The incidence of CMV infection in post-transplant patients can be 30-50%, therefore, prophylactic treatment of CMV is one of the important measures after transplantation.
III. Treatment
1. Treatment procedures for pulmonary infiltrates in immune-compromised hosts ICH with pulmonary infiltrates and fever are usually the first consideration for the possibility of infection. When the condition is less urgent, most anti-microbial therapy should be started after a clear etiologic diagnosis. Since the significance of radiographic imaging for etiologic diagnosis is very limited, a combination therapy regimen targeting positive, negative, and atypical pathogens should be aggressively pursued in severe and life-threatening cases, along with MRS or fungal therapy when indicated. Anti-infective therapy should be initiated after basic completion of sampling of pathogen examination specimens, and invasive sampling should be considered as early as possible if clinical signs are not contraindicated. The treatment procedure for infiltrative lung shadowing in immune-compromised hosts is shown in Figure 1.
2, Patients with ICH whose lung infection is clear from immune reconstitution should discontinue cytotoxic or antimetabolic drugs, glucocorticoids should be slowly withdrawn, and anti-organ rejection drugs should be used in reduced doses as appropriate.
3, empirical treatment of pulmonary infection in patients with ICH is different for different types of ICH when their empirical treatment is different. Pulmonary infections in patients with humoral immunodeficiency, including complement deficiency and splenectomy, are most common with Streptococcus pneumoniae and Haemophilus influenzae. Antimicrobial therapy should target these pathogens, such as ceftriaxone, respiratory fluoroquinolones, and in combination with epidemiological or therapeutic response, vancomycin or linezolid. Cellular immune damage complicated by pulmonary infection because of the higher chance of infection by specific pathogens (fungi, mycobacteria, viruses, protozoa), in principle, the pathogenic diagnosis should be clarified before treatment, and empirical treatment can be started immediately if Pneumocystis carinii, or cytomegalovirus infection is suspected. For post-transplant patients, in principle, preventive treatment against such pathogens can be taken.
4. Application of hormones or early organ transplantation. The first line of empiric treatment choice remains antimicrobial therapy. For those with severe disease, the principles of antibiotic use are.
(1) Antibiotics should be broad-spectrum, combined, in adequate doses, and administered intravenously.
(2) Use highly targeted antibiotics.
(3) Specimen collection for general pathogen testing should be completed before the first dose of antibiotics is given to facilitate later adjustment of antibiotics based on drug sensitivity results. Combination therapy with drugs targeting positive, negative and atypical pathogens is recommended. Since Pseudomonas aeruginosa and MRSA are common pathogens in this group of patients, initial therapy should cover these pathogens. As to whether to cover fungi, or other specific pathogens, a conclusion needs to be reached in the context of a comprehensive individual analysis.
Ninety-five percent of pulmonary infections after solid organ transplantation occur within one month after surgery, and the causative agents are similar to those of general thoracic or laparotomy, with S. pneumoniae and E. coli prevalent, or due to sepsis caused by indwelling intravenous catheters. From 1 to 6 months postoperatively, due to the high dose of immunosuppressive drugs, viral and opportunistic pathogenic infections are likely to occur. Pulmonary infections occurring after 6 months postoperatively may be related to the dose of immunosuppressive drugs needed, the occurrence of post-transplant lymphoproliferative disorder (PTLD), and other factors that predispose to opportunistic or tuberculosis infections. If only a small dose of immunosuppression is required, the risk of infection is significantly lower.
Fourth, for those whose disease is not very severe it is necessary to base
1.Estimation of pathogenic diagnosis.
2.Evaluation of clinical condition
3.Past medication use.
4.The functional status of the body.
5.Economic considerations and other comprehensive factors in the selection of anti-infective drugs.
For pulmonary infections with granulocytopenia or deficiency, anti-infective drugs can be selected by referring to the corresponding guidelines, and antifungal therapy can be given empirically when antibacterial therapy is not effective. Antifungal treatment can be based on relevant guidelines.
Within 30 days after bone marrow transplantation, fungal infections are the main causative agent, and antifungal drugs such as voriconazole or 2-gonadotropin B, which have the ability to target Aspergillus, are generally used. In infections occurring from 3O to 100 days, viruses, especially CMV, are the main ones, and the combination of corticosteroids and ganciclovir is generally used. It is advisable to monitor CMV-DNA after transplantation, and when indicated, antiviral therapy should be given promptly. After 100 days of transplantation, autologous transplant patients have basically recovered their humoral and cellular immunity and have little chance of complicating infections, while some allograft patients have reduced resistance to various viruses and enveloping bacteria (e.g., Haemophilus influenzae, Streptococcus pneumoniae) due to chronic graft-versus-host reactions. Therefore, if a pulmonary infection occurs then drugs targeting such pathogens may be prioritized for initial treatment.
Pneumocystis carinii pneumoniae (PCP) is also an important pathogen of pulmonary infections in patients with ICH. SMZco is an effective drug for PCP.
An increased proportion of mixed infections is also a feature of pulmonary infections in this group of patients, which can account for 10-15%. A common combination is a bacterial infection in addition to a viral or fungal infection. The higher incidence is due to cytomegalovirus, Aspergillus, combined with mixed infections caused by Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. Therefore, for severe cases, it is often a combination of multiple drugs, which may cause waste of drug use or increase the economic burden of patients, but if targeted drugs are not used in the beginning stage, it may increase the rate of death, which is currently a medical problem.
1, immune enhancing drugs such as BCG, thymidine, interferon, etc. can be used as appropriate. Granulocytopenia can be treated with leukocyte infusion; and granulocyte or granulocyte-monocyte colony-stimulating factor.
2.Strengthen supportive therapy and symptomatic treatment supportive therapy nutrition, cardiopulmonary function and psychological support are very important.
3.Strengthen the preventive measures of infection.
Such as strict sterilization of medical equipment, strict control of the indications for glucocorticoids and control of the use of immunosuppressive agents.
4, the preventive use of drugs currently has a certain evidence-based preventive drugs such as the preventive use of antifungal treatment and preventive treatment against PCP. For example, SMZco has been effective in preventing PCP in patients after solid organ transplantation.
5, on mechanical ventilation should be taken to lung protective mechanical ventilation methods.