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Reverse isolation for neutropenic patients
Abstract
Hospitalized patients with neutropenia are commonly placed in reverse isolation intended to protect them from acquiring serious infections. This step often causes confusion and anxiety for patients, families, and health care workers. We reviewed the evidence for efficacy of various types of reverse isolation in select patient groups. Reverse isolation in laminar air flow or high-efficiency particulate air (HEPA)-fltered rooms reduces the incidence of infection and may improve survival for patients receiving allogeneic bone marrow or stem cell grafts. Patients with acute leukemia, aplastic anemia, or other conditions characterized by similarly severe and prolonged neutropenia have also been shown to develop fewer infections when kept in laminar air flow or HEPA-filtered rooms during treatment; however, survival is probably not improved for these patients. Patients receiving chemotherapy for solid tumors or lymphoproliferative diseases who become neutropenic have not been shown to benefit from reverse isolation the way that it is practiced in most hospital settings. Therefore, the practice should be discouraged in the management of these patients.
... Reverse isolation of hospitalized patients with acute leukaemia is common practice to protect them from serious infection. Although the evidence to support this practice is limited (Nirenberg et al, 2006b), a recent systematic review concluded that managing leukaemia patients in laminar air flow or HEPA isolation rooms contributes to reduced morbidity and possibly mortality (Seshadri and Baumann, 2008). ...
Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored.
Large randomized controlled trials have shown significant decrease in incidence of invasive fungal infection in acute myeloid leukemia patients with Posaconazole prophylaxis. However, very less is known about value of Posaconazole prophylaxis in resource limited settings. This observational cohort study evaluated the incidence of fungal infection in patients with hematological malignancies undergoing induction chemotherapy with Posaconazole as antifungal prophylaxis and was compared with historical controls who received Fluconazole as fungal prophylaxis. The study was conducted from Oct 2013 to July 2015 in Department of Hematology of a tertiary care center. Fifty-three patients of acute myeloid leukemia on Posaconazole as fungal prophylaxis and 53 historical controls on Fluconazole as fungal prophylaxis were included for final analysis. Baseline characteristics were well matched between groups. Patients on Fluconazole were more likely to experience breakthrough IFDs (28.3 and 11.3%; p = 0.028) than in patients receiving Posaconazole prophylaxis. No significant difference was observed in overall, attributable mortality or in shift to first line antifungal. Both Posaconazole and Fluconazole were well tolerated with no major adverse effects requiring discontinuation of the drug. Minor side effects were seen in 39 and 47% patients in study and control group respectively. Vomiting and nausea were the commonest side effects seen in both study and control group (26 vs. 34% and 38 vs. 40% of patients, respectively). The results of our study in patients with acute myeloid leukemia provide evidence that Posaconazole prophylaxis significantly decreases the incidence of fungal infection and is well tolerated.
Despite significant advances in the prevention, diagnosis, and treatment of infection in the immunocompromised host, it remains a major cause of morbidity, increased length of stay, total costs, and of course mortality. Intensive care mortality rates are significantly higher among immunocompromised hosts in part due to the higher incidence of infection severity. The superimposition of the compromised host defenses and critical illness makes the detection and management of infections in such patients more difficult, but crucial toward salvaging patient outcome. Moreover, although there is a rapidly increasing evidence base in intensive care medicine, many interventional trials for the management of severe sepsis (activated protein C, adjunctive corticosteroids, goal-based resuscitation), acute lung injury (low stretch ventilation), and other organ failures have excluded immunocompromised hosts.
The efficiency of protective isolation and protective isolation plus gastrointestinal decontamination on the control of infectious complications in patients with decreased defence capacity was investigated prospectively in a cooperative trial with the participation of clinical centers in several European countries (European Organization for Research on Treatment of Cancer, Gnotobiotic Project Group). The study was performed in patients with acute leukemia under remission-induction therapy on the basis of the frequency of such patients in the participating centers. Over a period of five years, 137 cases of acute leukemia were randomly allocated to three different treatment groups as follows: Group A: strict protective isolation in plastic isolation systems or laminar air flow isolators and prophylactic antimicrobial decontamination by non-absorbable antibiotics, Group B: strict isolation alone in one or the other type of isolator, and Group C: routine hospital ward. The results demonstrated that the incidence of contamination and colonization with new bacteria could be decreased significantly by strict protective isolation alone and even more markedly by strict protective isolation and antimicrobial decontamination. They also demonstrated that in Group A there were less frequent episodes of severe infection. More specifically, the incidence of pulmonary infection was reduced significantly in both Groups A and B in comparison with Group C. The remission rate of acute leukemia was higher in patients of Groups A and B versus Group C (69%, 61%, 49%), although this result was not significant. However, the microbiological investigations and the outcome of the study suggest that the techniques of protective isolation and antimicrobial decontamination have to be improved to decrease further the incidence of infection in the compromised host.
Fifty-one evaluable patients with malignant sarcomas were randomly allocated to receive three courses of remission induction chemotherapy with cyclophosphamide, vincristine, Adriamycin, and dimethyl triazeno imidazole carboxamide (CYVADIC) on the protected environment-prophylactic antibiotic (PEPA) program24 or as controls.27 The complete remission rate was 33% for the PEPA group and 15% for the control group (P = 0.22). The response rates (complete plus partial) were 71% and 67%, respectively. The durations of response were similar for both groups of patients, but the PEPA patients survived substantially longer (median, 84 weeks vs. 58 weeks). The frequency of infection was significantly lower among the PEPA patients, and the doses of CYVADIC could be escalated more often among these patients. Dosage escalation was associated with a higher complete remission rate and lower fatality rate.
A prospective study of infectious morbidity in patients with acute myelocytic leukemia receiving chemotherapy was undertaken to test the effects of a reduction of ambient and/or endogenous microorganisms. Patients were randomly allocated to receive: (1) neither barrier isolation nor antimicrobial suppression; (2) antimicrobial suppression (gentamicin, vancomycin, and nystatin) in conventional ward reverse isolation; (3) barrier isolation and filtered air; or (4) barrier isolation, filtered air, and antimicrobial suppression. The presence of infection at the time of randomization was a significant factor (p < 0.02) accounting for an increased death rate. Individuals housed in the isolator who were initially uninfected demonstrated a decrease in the acquisition of severe infections after 23 study days, and fewer respiratory infections throughout the study period. Pseudomonas infections were decreased in isolator patients. Fewer fatalities from infection, but more from hemorrhage, were noted in patients who received endogenous antimicrobial suppression. An increased remission rate was seen in isolated patients not receiving antibiotics for gut flora suppression (not statistically significant). Significant improvement of leukemic remission rate or survival by these environmental manipulations was not found.
Laminar air flow isolation and decontamination procedures were evaluated in a prospective randomized study in patients with aplastic anemia or acute leukemia undergoing marrow transplantation from HLA-matched siblings. Patients transplanted in the laminar air flow group had significantly less septicemia and major local infections than did patients in the control group. Nineteen of 46 laminar air flow patients and six of 44 control patients are alive at present. In patients with aplastic anemia the survival was 13 of 17 in the laminar air flow group compared with four of 17 in the control group. In patients with acute leukemia the survival was six of 29 in the laminar air flow group versus two of 27 in the control group. These differences were not statistically significant. Death in both the laminar air flow and control groups was predominantly due to interstitial pneumonitis or recurrent leukemia, which were unaffected by isolation and decontamination.
113 patients being treated for acute non-lymphoblastic leukaemia were investigated to determine the effect of suppression of body microbial flora on prevention of infection. They were randomly allocated to a control group or a group which received non-absorbed antibiotics by mouth and topical applications of cutaneous and mucosal antiseptic preparations. The group receiving oral non-absorbed antibiotics had significantly few infections, fewer deaths from infection, fewer pyrexial episodes, and consequently received less systemic antibiotic therapy than the controls.
Fifty-eight patients with malignant lymphoma were randomly allocated to receive three courses of chemotherapy to induce remission with CHOP-Bleo on the protected environment-prophylactic antibiotic (PEPA) program (30 patients) or as controls (28 patients). The complete remission rate for all patients was 74 per cent, for patients with diffuse histiocytic lymphoma 78 per cent and for patients with nodular poorly differentiated lymphocytic lymphoma 65 per cent. There were no significant differences in response rates and duration of responses between those on the PEPA program and control patients. The frequency of infection was significantly lower among the patients on the PEPA program, and dosage escalation of the chemotherapeutic agents was accomplished more often among these patients. Dosage escalation did not increase the complete remission rate, but it did reduce the relapse rate and signficantly reduced the fatality rate. The duration of remission and survival was significantly longer for those patients who received dosage escalation.
One hundred and forty-five adults with acute leukemia were randomized to receive remission induction therapy in or out of a protected environment (PE) with prophylactic antibiotics orally (PA) or systemically (SA). Sixty-three patients were randomized in PE and 82 outside a PE. The proportion of patients who survived long enough to receive an adequate trial was higher in the PE (97%) than out (82%) (P = .01). The complete remission (CR) rate was 71% in and 43% out of the PE (P less than .01). Fifty-five patients received PA and 90 received SA. The CR rates were 61% and 45%, respectively. Of the 145 patients, 73 (50%) developed 102 episodes of major infections. Twenty-six of 63 patients in the PE developed major infection compared to 47 of 82 outside a PE (P = .08). The incidence rate of 13% fatal infections in a PE was significantly smaller than the 28% rate outside a PE (P = .04). The number of days with infections at less than 500 neutrophils/mm3 was also significantly lower inside a PE than outside (P less than .01). When comparing patients receiving SA or PA, there was no statistically significant difference in the incidence of infections. Forty-one patients received OAP Chemotherapy and 104 received adriamycin-OAP plus BCG. The CR rate on OAP was 44% compared with 60% on Ad-OAP + BCG. Infection rates were 76% and 40%, respectively (P less than .01). The median survival time was 72 weeks for patients in PE compared with 42 weeks for patients outside a PE (P less than .01). The prophylactic antibiotic regimens were well tolerated by most patients. This prospective randomized study has demonstrated statistically significant advantages for a lowered risk of fatal infection, higher CR rate and longer survival of patients treated in a PE with prophylactic antibiotics compared with patients treated in a conventional hospital room. Also, there was evidence for the superiority of adriamycin-OAP + BCG treatment compared with OAP.
Reverse isolation and prophylactic oral nonabsorbable antibiotics were evaluated among 64 consecutive noninfected adults with acute nonlymphocytic leukemia admitted for remission induction. Patients were randomly allocated to laminar air flow room reverse isolation with oral nonabsorbable antibiotics (LAF plus A), routine hospital ward care with antibiotics (W plus A), or ward care alone (W). The LAF plus A patients had a significantly decreased incidence of total infection, bacteremias, pneumonias, rectal abscesses, urinary tract infection, and pharyngitis. Infectious deaths were reduced in the LAF plus A group and the time to the first infection or to fatal infection was delayed. The W plus A patients who regularly ingested the antibiotics had a reduction in infections similar to that of the LAF plus A patients but those who could not tolerate the antibiotics had an incidence of infection comparable to the ward patients. The LAF plus A and the W plus A patients also had higher complete remission rates and longer median survival than the unprotected ward patients.
Three hundred and forty-two patients with hematological malignancies underwent allogeneic marrow transplantation from family donors and were allocated to receive 1) no specific infection prophylaxis in a conventional hospital room (control, 100 patients), 2) prophylactic systemic antibiotics (PSA) in a conventional hospital room (PSA group, 101 patients), 3) decontamination and isolation in a laminar air flow (LAF) room (LAF group, 65 patients) and 4) PSA in an LAF room (LAF+PSA group, 76 patients). Patients were studied for bacterial and fungal complications from the day of admission and until engraftment. LAF isolation was discontinued before engraftment in 27% (LAF+PSA group) to 32% (LAF group) of isolated in 26% (LAF+PSA group) to 27% (PSA group) of patients on prophylactic antibiotics. Septicemia occurred in 41%, 22%, 25% and 10% of patients in the control, PSA, LAF and LAF+PSA group, respectively. The incidence of septicemia was significantly less in the LAF+PSA group than in the control and LAF group with the incidence of septicemia significantly higher in the control group than in any of the other three groups. No other risk factors analyzed in proportional hazards regression tests were associated with septicemia acquisition. It is concluded that effective infection prevention modalities significantly reduce infection morbidity in transplant patients. Since most granulocytopenic transplant patients not receiving PSA will receive empiric or therapeutic broad spectrum antibiotics. The use of PSA in or out of LAF isolation is recommended as an effective modality to reduce septicemia acquisition.
99 patients with hematological malignancies underwent allogeneic marrow transplantation from HLA-identical sibling donors and were randomized to receive one of two forms of infection prophylaxis while granulocytopenic: (1) prophylactic systemic antibiotics in a conventional hospital room (PSA, 50 patients) or (2) decontamination, isolation in a laminar air flow room and the administration of prophylactic systemic antibiotics (LAF + PSA, 49 patients). Only 1 patient (3%) in the LAF + PSA group acquired septicemia while granulocytopenic compared to 11 (24%) patients in the PSA group (p less than 0.005). Three patients (6%) in the LAF + PSA group acquired major localized infections compared to 9 (18%) in the PSA group (p = 0.06). There was no significant difference in days in hospital post transplant, days of granulocytopenia, days of fever, incidence of acute graft-versus-host disease, interstitial pneumonitis or overall survival. We conclude that the use of prophylactic systemic antibiotics added to decontamination and laminar air flow isolation of patients undergoing marrow transplantation significantly reduces the incidence of septicemia in the granulocytopenic period.
To test the hypothesis of whether high doses of chemotherapy in combination achieve higher response rates and longer durations of response and survival, we treated 33 pre- and perimenopausal patients with good performance status in a prospective trial with escalating doses of fluorouracil, doxorubicin and cyclophosphamide (FAC). Patients were randomly assigned to be treated within a protected environment (laminar air flow room), with prophylactic antibiotics, or in a standard hospital room. Important patient characteristics were equally distributed in the two treatment arms. A major objective response was observed in 27 of the 32 evaluable patients (84%), and 11 (34%) achieved a complete remission (CR). There was no significant difference in overall and complete response rates between the two treatment arms, nor was there a substantial difference in times to progression or survival between the groups treated in or out of the protected environment. Comparison of the results of this study with previously reported programs of FAC chemotherapy in patients with metastatic breast cancer shows that this study achieved higher overall and complete response rates. However, neither the time to progression, nor the survival of responders or the entire patient group was different from our previous experience with standard FAC chemotherapy. When the study was initiated in 1976, the proposed dose escalation represented high-dose chemotherapy. In retrospect, even the "high" doses used in this study represent only a modest increase over standard doses of chemotherapy. Much steeper dose escalations will be needed to evaluate the efficacy of high-dose chemotherapy in breast cancer, as well as the protective value of the protected environment and prophylactic antibiotics in metastatic breast cancer.
Fifty-nine evaluable patients under 65 years of age with measurable metastatic breast cancer and without prior chemotherapy were randomly assigned to treatment with fluorouracil, Adriamycin (Adria Laboratories, Columbus, OH), and cyclophosphamide (FAC) at standard or high doses (100% to 260% higher than standard FAC) following a dose escalation schedule. Patients randomized to the high-dose FAC received the first three cycles of therapy within a protected environment. Subsequent cycles for this group were administered at standard doses of FAC in an ambulatory setting, the same as for the control group. After reaching 450 mg/m2 of Adriamycin, patients in both groups continued treatment with cyclophosphamide, methotrexate, and fluorouracil until there was disease progression. Analysis of pretreatment patient characteristics showed an even distribution for most known pretreatment factors, although the control group had slightly (but nonsignificantly) more favorable prognostic characteristics. Fourteen patients (24%) achieved a complete remission (CR) and 32 (54%) achieved a partial remission (PR), for an overall major response rate of 78%. There were no differences in overall, CR, or PR rates between the high-dose FAC and control groups. The median response durations were 11 and 10 months for the protected environment and control groups, respectively, and the median survival was 20 months for both groups. Hematologic, gastrointestinal (GI), and infection-related complications were significantly more frequent and severe in the group treated with high-dose chemotherapy. Stomatitis, diarrhea, and skin toxicity were dose-limiting. However, there were no treatment-related deaths. High-dose induction combination chemotherapy with the agents used in this study failed to increase the response rate or survival duration, and resulted in a substantial increase in toxicity.
To reduce the frequency of infection in acute leukemia, we employed isolation and air-filtration facilities ("protected environment") and a prophylactic regimen that included oral nonabsorbable antibiotics. Eighty-eight randomized patients received identical remission-induction chemotherapy within one of three groups: protected environment combined with the prophylactic regimen (Group 1); oral nonabsorbable antibiotics alone (Group 2); and neither isolation nor prophylaxis (Group 3). The groups were comparable in factors that might influence the course of leukemia and susceptibility to infection. Environmental maneuvers. were effective in reducing the potential inoculum of ambient micro-organisms. Patients in Group 1 had 1/2 as many severe infections as those in Groups 2 and 3. Whereas approximately 1/4 of the patients in Groups 2 and 3 died of infection while on study, none in Group 1 died for that reason. Despite fewer infections in Group 1, no intergroup differences were found in remission rat...
One hundred one patients with severe aplastic anemia underwent allogeneic marrow transplantation and received one of three forms of infection prophylaxis: oral nonabsorbable antibiotics and isolation and decontamination in a laminar airflow room (36 patients); prophylactic granulocyte transfusions from a single family member donor (33 patients); or conventional treatment in single rooms with hand-washing and mask precautions (31 patients). During the period of granulocytopenia, patients in the laminar airflow rooms acquired fewer infections than either of the other groups, but this difference was statistically significant only when compared with the group receiving conventional treatment. Patients in the laminar airflow rooms had significantly fewer infections after engraftment as compared with the other two groups. Incidence of interstitial pneumonia and graft rejection was not different among the three groups. Acute graft-versus-host disease occurred later (Day 47) in the group in the laminar airflow rooms as compared with the group receiving prophylactic granulocyte transfusions (Day 23) or the group receiving conventional treatment (Day 20). The incidence of grades II to IV acute graft-versus-host disease was less in the patients in the laminar airflow rooms but only reached borderline significance (p = 0.08) when compared with the conventionally treated patients. The survival at Day 100 was 92 percent for the group in the laminar airflow rooms, 79 percent for the group receiving prophylactic granulocyte transfusions, and 64 percent for the group receiving conventional treatment.
Fever, clinical infection, bacteriologically documented infection, and death from infection were evaluated in 95 consecutive uninfected patients with severe granulocytopenia (less than 0.5 x 10(6)/liter). Patients were randomly allocated to reverse isolation and prophylactic oral nonabsorbable antibiotics or to open ward care. The microbiologic surveillance of air samples and stool cultures showed reduction of pathogenic organisms in patients treated in protective environment units. There was a statistically significant reduction in the incidence of fever (80% vs. 39.6%; P less than 0.001), clinical infections (55.3% vs. 25%; P less than 0.01), bacteriologically documented infections (53.2% vs. 20.8%; P less than 0.01), and deaths from infections (25.5% vs. 8.3%; P = 0.02) in patients treated in a protective environment as compared with patients treated on the open ward.
To assess the value of simple protective isolation, we prospectively compared it with standard hospital care in 43 episodes of severe granulocytopenia, most occurring in patients with acute nonlymphocytic leukemia. Sterilized food and prophylactic oral antibiotics were not used. Twenty episodes in 17 patients were randomized to simple protective isolation (437 days), and 23 episodes in 20 patients to standard care (611 days). No statistically significant differences were observed in the overall incidence of infection, time to onset of first infection, or days with fever. Twenty-seven infections occurred in recipients of standard care (4.42 per 100 days), and 28 infections in isolated patients (6.41 per 100 days). Except for a threefold higher rate of bacteremia in patients in isolation (2.06 vs. 0.65 per 100 days), the profile of infection was similar in the two groups. Neither response to antileukemic therapy nor survival was improved by isolation. We conclude that protective isolation alone, as practiced in most hospitals, appears not to benefit granulocytopenic patients.
Fifty-one valuable patients with malignant sarcomas were randomly allocated to receive three courses of remission induction chemotherapy with cyclophosphamide, vincristine, Adriamycin, and dimethyl triazeno imidazole carboxamide (CYVADIC) on the protected environment-prophylactic antibiotic for the control group (P = 0.22). The response rates (complete plus partial) were 71% and 67%, respectively. The durations of response were similar for both groups of patients, but the PEPA patients survived substantially longer (median, 84 weeks vs. 58 weeks). The frequency of infection was significantly lower among the PEPA patients, and the doses of CYVADIC could be escalated more often among these patients. Dosage escalation was associated with a higher complete remission rate and lower fatality rate.
Various isolation strategies are used to prevent infections during bone marrow transplantation; data on their efficacy are lacking. We studied whether use of high efficiency particulate air filtration (HEPA) and/or laminar airflow (LAF) units affect transplant-related mortality (TRM) or survival in the first year after allogeneic transplantation. 5065 patients with leukemia receiving bone marrow transplants from an HLA identical sibling (n = 3982) or alternative related or unrelated donors (n = 1083) between 1988 and 1992 were reported to the International Bone Marrow Transplant Registry by 222 teams. Two types of isolation were considered: (1) conventional protective isolation with single patient room and any combination of hand-washing, gloves, mask and gown; and (2) HEPA and/or LAF. Cox proportional hazards regression models were used to determine the relative risks (RRs) of transplant-related mortality (TRM) and of deaths from any cause in patients treated in HEPA/LAF units compared to patients treated in conventional isolation. HLA-identical sibling and alternative donor transplants were analyzed separately. Risks of TRM and overall mortality in the first 100 days post-transplant were significantly lower among patients treated in HEPA/LAF units than in those treated conventionally. RRs of TRM were 0.76 (P = 0.009) for recipients of HLA-identical sibling transplants and 0.65 (P = 0.003) for recipients of alternative donor transplants. Correspondingly RRs of overall mortality were 0.80 (P = 0.02) and 0.65 (P = 0.0006). Decreased risks of TRM and of death in the first 100 days post-transplant resulted in significantly higher 1-year survival rates in patients treated in HEPA/LAF rather than in conventional isolation units. Use of HEPA and/or LAF to prevent infections decreases TRM and increases survival after allogeneic bone marrow transplants for leukemia.
To describe institutional practices related to dietary restrictions for patients with neutropenia to determine whether restrictions are used and when they are implemented and discontinued.
Descriptive survey.
156 institutions belonging to the Association of Community Cancer Centers.
Mailed survey.
Of the institutions surveyed, 78% (n = 120) placed patients with neutropenia on restricted diets. Participating institutions responded that patients were placed on restricted diets at a variety of different white blood cell and neutrophil counts, including neutrophils < 1,000 (43%) and < 500 (46%). The majority of institutions (92%) placed patients on restricted diets once neutropenia was documented, while only 9% of institutions restricted diets when cancer treatment was initiated. Of the participating institutions, 83% (n = 96) restricted diets only when patients were neutropenic rather than throughout the duration of the chemotherapy regimen. The most commonly restricted foods were fresh fruits and juices (92%), fresh vegetables (95%), and raw eggs (74%). Few institutions restricted tap water (12%). Wine was restricted at 39% of institutions, and beer was restricted at 40% of institutions.
The role of diet in the development of infection in patients with neutropenia is unclear. This unclear role contributes to the variation in dietary restrictions among institutions.
Additional research should focus on dietary factors contributing to neutropenic infections and establishing criteria for implementation of specific dietary modifications. Nursing assessment should include nutritional status and risk factors for neutropenia and bacterial translocation. Nursing protocols for neutropenic dietary restrictions should be based on research findings.