| Background:Blood cancers includes leukemia, lymphoma, multiple myeloma and myelodysplastic syndrome. In recent years, with extensive use of high dose chemotherapy, more and more fungal infections appeared in the blood cancer patients. Invasive pulmonary fungal infection (IPFI) is the most common and increasingly becoming an important cause of death. Analysis of risk factors of IPFI in blood cancer patients and discussion of the effective preventive measures are the key to control IPFI and become hot issues for researchers .At present, the studies on the prevention of the IPFI are mainly concentrated in the oral or intravenous systemic antifungal drug , but the results are inconsistent . In additional, systemic administration will induce the inevitable side effects, drug resistance and increased costs and other issues. Therefore, it is very important to look for an effective, inexpensive and convenient way with low side effects to prevent IPFI. Fungal colonized in the oropharyngeal easily invade to the lower respiratory tract and cause IPFI in blood cancer patients with low immunity and chemotherapy. Thus theoretically speculated, pulmonary fungal may come from oropharyngeal, and using effective mouth rinse can reduce the occurrence of IPFI. But no experimental study has confirmed it.some Clinicians and nurses tried to prevent the respiratory fungus infection by using sodium bicarbonate solution for mouth rinse or wet fluid for artificial airway, but the results are also inconsistent and need further studies. Nystatin has a broad antifungal spectrum with low resistance and no absorption as mouth rinse. It is safety for patients and it is also more cheaper. At present, some Clinicians empirically use 1% nystatin solution as mouth rinse to prevent or treat IPFI, but the exact effect need be further confirmed.The research included three parts:1. A Cohort Retrospective StudyThe clinical data of IPFI cases of blood cancer non-HSCT patients admitted to the Union Hospital affiliated to Fujian Medical University from 1 January 2008 to 31 December 2009 were collected. The incidence,the distribution of fungi pathogenies , and the risk factors of IPFI related to blood cancer non-hematopoietic stem cell transplant (HSCT) were retrospectively analyzed. The cases of proven and probable IPFI were taken as the observation group. The patients with pulmonary bacterial infection and the patients without pulmonary infection were Respectively taken as the control groups. The statistics methods of the Logistic univariate and multivariate analysis were used.2. Experimental study of molecular biologyThe study is to analyze the source of the fungi of IPFI in blood cancer patients , by detecting fungi'26S rDNA ITS region gene sequences and polymorphism analysis . The specimens from the patients'pharynx, lung,nose and digestive tract were firstly test for culture and morphological identification of fungi. The method of glass beads was used for extraction of fungal DNA, and PCR amplification and sequencing analysis of fungal 26S rDNA ITS sequence polymorphism were used for identification of fungi strains.3.A Clinical prospective studyTo compare and discuss the preventive effect of the nystatin mouth rinse , the sodium bicarbonate solution and normal saline rinse for IPFI in blood cancer patients. Main Results1.IPFI incidence and distribution of the fungiThere is a total of 6047 cases of blood cancer patients from 1January 2008 to 31December 2009. 212 cases met the diagnosis criteria of IPFI,including 1 proven case and 105 probable cases and 106 possible cases. The overall incidence rate of IPFI is 3.5%. Candida albicans and aspergillus respectively accounted for 50.7% and 37.3%.2. Risk factorsTo lung bacterial infection as the control group, the Logistic univariate and multivariate analysis showed that with previous IPFI (OR 6.721, 95% CI 1.733 ~ 26.062), length of hospital stay (OR 5.582, 95% CI 2.792 ~ 11.159), Hypoproteinemia (OR 4.686, 95% CI 2.103 ~ 10.440), bacterial sepsis (OR 4.545, 95% CI 1.058 ~ 19.525), Agranulocytosis (OR 3.310, 95% CI 1.408 ~ 7.781) And age (OR 1.618, 95% CI 1.023 ~ 2.559) were the risk factors of IPFI in blood cancer patients . Nystatin mouth rinse is the protective factor for IPFI (OR 0.202, 95% CI 0.122 ~ 0.334)。To the control group of no pulmonary infection , the Logistic univariate and multivariate analysis showed that length of hospital stay (OR 15.862, 95%CI 4.351 ~ 57.830), previous IPFI (OR 13.292, 95% CI 1.768 ~ 99.917),The number of antibiotics (OR 11.212, 95%CI 3.585 ~ 35.071), hypoalbuminemia (OR 7.505, 95%CI 1.887 ~ 29.851), Agranulocytosis (OR 6.885, 95%CI 1.342 ~ 35.321) and the age (OR 2.303, 95%CI 1.145 ~ 4.632) were the risk factors for IPFI. Nystatin mouth rinse is also the protective factor for IPFI (OR0.075, 95% 0.027 ~ 0.210). However, gender, blood cancer type and disease status , diabetes, chronic obstructive pulmonary (COPD), liver disease , oral fungal infections, intestinal fungal infection, parenteral nutrition, days of antibiotics, and glucocorticoids were not independent risk factors of IPFI in blood cancer patients .3. 96.7% (29/30) of patients were isolated the same fungi strains from their pharynx , and pulmonary. Among the 29 patients, 25 patients were identified with Candida albicans (from eight different strains),and 4 patients were respectively identified with Candida krusei, Candida glabrata, Candida tropicalis and Clavispora lusitaniae .In additional , the results show different in another patient. Candida albicans were detected in the pharyngeal and faecal samples of the patient, but Aspergillus flavus were isolated in the samples of sputum and nasal secretions. The Aspergillus flavus from the sputum and the nasal secretions have the same 26S rDNA ITS sequencies. 84.6% (11/13) of patients isolated the same fungi strains from their pharynx and digestive tract. 76.9% (10/13) of patients isolated the same fungi strains from their pumonary and digestive tract. 4. The IPFI rate in the nystatin mouth rinse group was 1.6%, significantly lower than 27.7% of the saline mouth rinse group and the sodium bicarbonate mouth rinse group16.3% (P <0.05). The IPFI incidence in Sodium bicarbonate mouth rinse group was also significantly lower than the saline gargle group (P <0.05). Nystatin rinse group of intestinal fungal infection rate was 1.6%, significantly lower than the saline rinse group 12.8% and 14.3% of the Sodium bicarbonate rinse group (P <0.05)Main Conclusions1.Candida albicans is still the most common fungi of IPFI in blood cancer non-HSCT patients. the related risk factors are Age, length of hospital stay, previous IPFI , hypoproteinemia, glucocorticoids≥10 days, bacterial sepsis and the number of antibiotics . Length of hospital stay and previous history are the highest risk.2. There is a high coisogenic of fungal from pharynx, lungs and digestive tract fungal in blood cancer patients. Pulmonary candidas mainly from the pharynx, and Aspergillus may be mainly from inhalation. Oral care interventions may be effective against pulmonary candidiasis.3. 1% nystatin mouth rinse and 2.5% sodium bicarbonate mouth rinse can achieve a certain effect on the prevention of IPFI in blood cancer patients , but the former is better than the latter. In additional, 1% nystatin mouth rinse can significantly reduce the incidence of intestinal fungal infection. The cost of nystatin is low , and adverse reaction was not found.
|
PDF Full Text Request