Tuberculous infections in patients with hematological disorders and hematopoietic stem cell transplant vary in incidence, complications and response to treatment. A retrospective study of patients with various benign and malignant hematological disorders and recipients of hematopoietic stem cell transplant who were treated at Riyadh Armed Forces Hospital, Saudi Arabia between January 1991 and December 2002 and who developed tuberculous infections was conducted. Tuberculous infections occurred in eighteen patients with hematological disorders and hematopoietic stem cell transplant. The main associated factors were: reduced immunity due to the primary hematological disorder, age more than 50 years and the administration of cytotoxic chemotherapy, steroids or radiotherapy. These infections frequently involved the lungs and predominantly occurred in males and in patients with chronic myeloproliferative disorders, myelodysplastic syndrome and acute myeloid leukemia. In patients treated with intravenous cytotoxic chemotherapy, tuberculous infections tended to occur earlier and also tended to be more disseminated compared to infections occurring in patients treated with oral chemotherapy. Anti-tuberculous treatment was given to 16 patients and it was successful in 15 of these patients. Tuberculous infections cause significant morbidity and mortality in patients with various hematological disorders and in recipients of hematopoietic stem cell transplant. The early administration of anti-tuberculous therapy and compliance with drug treatment are associated with successful outcomes while delayed management, drug resistance and the presence of miliary infections are associated with poor prognosis and high mortality rates.
Stenotrophomonas maltophilia (S. maltophilia) is a globally emerging Gram-negative bacillus that is widely spread in environment and hospital equipment. Recently, the incidence of infections caused by this organism has increased, particularly in patients with hematological malignancy and in recipients of hematopoietic stem cell transplantation having neutropenia, mucositis, diarrhea, central venous catheters or graft versus host disease and receiving intensive cytotoxic chemotherapy, immunosuppressive therapy or broad-spectrum antibiotics. The spectrum of infections in hematopoietic stem cell transplantation recipients includes: pneumonia, urinary tract and surgical site infection, peritonitis, bacteremia, septic shock and infection of indwelling medical devices. The organism exhibits intrinsic resistance to many classes of antibiotics including carbapenems, aminoglycosides, most of the third generation cephalosporins and other β-lactams. Despite the increasingly reported drug resistance, trimethoprim-sulfamethoxazole is still the drug of choice However, the organism is still susceptible to: ticarcillin-clavulanic acid, tigecycline, fluoroquinolones, polymyxin-B and rifampicin. Genetic factors play a significant role not only in evolution of drug resistance but also in virulence of the organism. The outcome of patients having S. maltophilia infections can be improved by: using various combinations of novel therapeutic agents and aerosolized aminoglycosides or colistin, prompt administration of in-vitro active antibiotics, removal of possible sources of infection such as infected indwelling intravacular catheters and application of strict infection control measures.
Nontuberculous mycobacteria (NTM) are acid-fast bacteria that are ubiquitous in the environment and can colonize soil, dust particles, water sources and food supplies. They are divided into rapidly growing mycobacteria such as Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium abscessus as well as slowly growing species such as Mycobacterium avium, Mycobacterium kansasii and Mycobacterium marinum. About 160 different species, which can cause community acquired and health care-associated infections, have been identified. NTM are becoming increasingly recognized in recipients of hematopoietic stem cell transplantation with incidence rates ranging between 0.4% and 10%. These infections are 50 to 600 times commoner in transplant recipients than in the general population and the time of onset ranges from day 31 to day 1055 post-transplant. They have been reported following various forms of hematopoietic stem cell transplantation. Several risk factors predispose to NTM infections in recipients of stem cell transplantation and these are related to the underlying medical condition and its treatment, the pre-transplant conditioning therapies as well as the transplant procedure and its complications. Clinically, NTM may present with: unexplained fever, lymphadenopathy, osteomyelitis, soft tissue and skin infections, central venous catheter infections, bacteremia, lung and gastrointestinal tract involvement. However, disseminated infections are commonly encountered in severely immunocompromised individuals and bloodstream infections are almost always associated with catheter-related infections. It is usually difficult to differentiate colonization from true infection, thus the threshold for starting therapy remains undetermined. Respiratory specimens such as sputum, pleural fluid and bronchoalveolar lavage in addition to cultures of blood, bone, skin and soft tissues are essential diagnostically. Susceptibility testing of mycobacterial isolates is a basic comp
Acinetobacter baumannii (A. baumannii) is a Gram-negative, strictly aerobic, non-fermentative coccobacillus which is widely distributed in nature. Recently, it has emerged as a major cause of health care-associated infections in addition to its capacity to cause community acquired infections. Risk factors for A. baumannii infections and bacteremia in recipients of hematopoietic stem cell transplantation include: severe underlying illness such as hematological malignancy, prolonged use of broad-spectrum antibiotics, invasive instrumentation such as central venous catheters or endotracheal intubation, colonization of respiratory, gastrointestinal or urinary tracts in addition to severe immunosuppression caused by using corticosteroids for treating graft versus host disease. The organism causes a wide spectrum of clinical manifestations, but serious complications such as bacteremia, septic shock, ventilator-associated pneumonia, extensive soft tissue necrosis and rapidly progressive systemic infections that ultimately lead to multiorgan failure and death are prone to occur in severely immunocompromised hosts. The organism is usually resistant to many antimicrobials including penicillins, cephalosporins, trimethoprim-sulfamethoxazole, almost all flouroquinolones and most of the aminoglycosides. The recently increasing resistance to carbapenems, colistin and polymyxins is alarming. Additionally, there are geographic variations in the resistance patterns and several globally and regionally resistant strains have already been described. Successful management of A.baumannii infections depends upon appropriate utilization of antibiotics and strict application of preventive and infection control measures. In uncomplicated infections, the use of a single active beta-lactam may be justified, while definitive treatment of complicated infections in critically ill individuals may require drug combinations such as colistin and rifampicin or colistin and carbapenem.
High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is considered the standard of care for multiple myeloma patients who are eligible for transplantation. The process of autografting comprises the following steps: control of the primary disease by using a certain induction therapeutic protocol, mobilization of stem cells, collection of mobilized stem cells by apheresis, cryopreservation of the apheresis product, administration of high-dose pretransplant conditioning therapy, and finally infusion of the cryopreserved stem cells after thawing. However, in cancer centers that treat patients with multiple myeloma and have transplantation capabilities but lack or are in the process of acquiring cryopreservation facilities, alternatively noncryopreserved autologous stem cell therapy has been performed with remarkable success as the pretransplant conditioning therapy is usually brief.
Mycobacterium tuberculosis (M. tuberculosis) infections are uncommon in recipients of hematopoietic stem cell transplantation. These infections are 10 to 40 times commoner in recipients of stem cell transplantation than in the general population but they are 10 times less in stem cell transplantation recipients compared to solid organ transplant recipients. The incidence of M. tuberculosis infections in recipients of allogeneic stem cell transplantation ranges between ˂ 1% and 15% and varies considerably according to the type of transplant and the geographical location. Approximately 80% of M. tuberculosis infections in stem cell transplant recipients have been reported in patients receiving allografts. Several risk factors predispose to M. tuberculosis infections in recipients of hematopoietic stem cell transplantation and these are related to the underlying medical condition and its treatment, the pre-transplant conditioning therapies in addition to the transplant procedure and its own complications. These infections can develop as early as day 11 and as late as day 3337 post-transplant. The course may become rapidly progressive and the patient may develop life-threatening complications. The diagnosis of M. tuberculosis infections in stem cell transplant recipients is usually made on clinical grounds, cultures obtained from clinical specimens, tissues biopsies in addition to serology and molecular tests. Unfortunately, a definitive diagnosis of M. tuberculosis infections in these patients may occasionally be difficult to be established. However, M. tuberculosis infections in transplant recipients usually respond well to treatment with anti-tuberculosis agents, provided the diagnosis is made early. A high index of suspicion should be maintained in recipients of stem cell transplantation living in endemic areas and presenting with compatible clinical and radiological manifestations. High mortality rates are associated with infections caused by multidrug resist