Effectiveness of a Specialized Emergency Department Unit for Cancer Patients in Management of Febrile Neutropenia

Transcription

1 대한응급의학회지제 21 권제 3 호 Volume 21, Number 3, June 2010 원 저 Effectiveness of a Specialized Emergency Department Unit for Cancer Patients in Management of Febrile Neutropenia Department of Emergency Medicine, Department of Internal Medicine 1, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea Shin Ahn, M.D., Kyung-Soo Lim, M.D., Won Kim, M.D., Tae-Won Kim, M.D. 1, Yoon-Seon Lee, M.D. Purpose: Our medical institute developed an emergency department (ED) cancer unit that specialized in the management of oncologic emergencies; it was named the cancer emergency room (CER). The object of our study was to determine improvements in patient management, especially management of febrile neutropenia (FN). Methods: This was a retrospective study of 137 febrile neutropenic episodes, including 70 episodes occurring between May 2008 and August 2008, and 67 episodes between May 2009 and August Episodes were grouped into two categories: those managed in the CER and those managed in the existing ED main treatment area of the main emergency room (MER). The time interval between presentation at the ED and first antibiotic administration, termed the door-to-needle time, clinical outcomes, and length of inpatient hospital stay were analyzed for those admitted. Results: The median door-to-needle time in the CER was 2 hours ( ), faster than the time, 3.5 hours ( ) in the MER (p=0.000). The length of inpatient hospital stay in the CER was 4 days (1-16), shorter than that, 6 days (1-51), in the MER (p=0.034). Twelve episodes (26.1%) had adverse events in the CER and 42 (46.2%) in the MER (p=0.023). Conclusion: Management of FN in a unit specialized for oncologic emergencies showed faster antibiotic delivery time, more favorable outcomes and shorter duration of admission. This specialized cancer unit in the ED enables prompt and relevant management in oncologic emergencies, including events related to chemotherapy toxicity. Key Words: Neoplasms, Fever, Neutropenia, Hospital emergency services, Anti-bacterial agents 책임저자 : 이윤선서울특별시송파구풍납2동 서울아산병원응급의학과, 긴급진료실 Tel: 02) , Fax: 02) ysdoc@amc.seoul.kr 접수일 : 2010년 1월 15일, 1차교정일 : 2010년 1월 25일게재승인일 : 2010년 2월 10일 347 Introduction Emergency department (ED) is a place gathered with heterogeneous population having various illnesses including infectious disease, and for the neutropenic patients, staying in ED with various other patients could lead to a potential threat of infection. Febrile neutropenia (FN) is a common complication of cancer chemotherapy. It is associated with considerable morbidity, mortality, and cost 1). The risk of infection is significantly increased in severely neutropenic patients, and many of the technologies and pharmacological tools used in modern medicine also have the potential to facilitate the onset of infection 2). Standard treatment for febrile neutropenic patient was hospitalization and treatment with broad-spectrum intravenous antibiotics 3,4). Although, this approach decreased mortality, routine hospitalization might have contributed in ED crowding, and which in turn could decline the quality of care for the patients. Diverse studies were performed to lessen the hospital stay of febrile neutropenic patients, especially for those who were at low risk for serious medical complications 5-8). However, routine clinical practice and eligibility for early hospital discharge and outpatient management is limited and poorly accepted. Since 2008, in Asan medical center, the number of patients visiting ED per month increased (5,850± in 2008 vs. 7,338±408.7 in 2009) and the proportion of cancer patients among them also increased (4.35±0.13% in 2008 vs. 6.35±0.53 in 2009). Crowded ED environment might have led to poor quality of care among cancer patients and other patients visiting ED. In May 2009, our institute set up an ED cancer unit, named cancer emergency room (CER), which was a part of the Cancer Center Operation began in April It was designed for

2 348 / 대한응급의학회지 : 제 21 권제 3 호 2010 focused and specialized management of oncologic emergencies, in order to improve quality of care and patient outcomes. The object of this study was to ascertain the effectiveness of the specialized ED unit for cancer patients on improvements of patient management, and to find whether this system improved patient outcomes, especially in the FN. Materials and Methods 1. Study design We performed a retrospective comparison study of all adult patients 15 years and older, who visited ED and diagnosed as FN from May 2008 to August 2008, and May 2009 to August These enrollment periods were chosen to examine the care before and after the introduction of the CER, during the same months in year. Patients were eligible if they had a histologically diagnosed cancer and FN as a result of chemotherapy. Episodes with a prior antibiotic administration before ED visit were excluded in the study. Neutropenia was defined as absolute neutrophil count (ANC) <500 cells/mm 3 or a count <1000 cells/mm 3 with a predicted decrease to <500 cells/mm 3 within hours and fever as oral temperature 38.0 C for at least one hour 9). This study was performed in a large, urban, tertiary-care ED with an emergency medicine residency program, and was approved by the Institute Review Board at Asan Medical Center. 2. Setting The ED has annual census of approximately 76,000 patients, with 50 beds. In May 2009, the CER was opened. It has monthly census of 360 patients and 18 beds are allocated. The CER is staffed by one board certified emergency physician, and one emergency medicine and one internal medicine resident work in turn. Cancer patients who were managed in Asan medical center oncologic department are eligible in the CER management, so the new visitors or those who were managed in other departments are not allocated. The CER has fixed number of 18 treatment beds, and after the patient reaching the fixed number by timely order, the remainders are allocated in preexisting ED main treatment area of the main emergency room (MER). 3. Data collection and processing Patients were grouped into two categories, one who were managed in the CER and the other who were managed in the MER. Upon arrival at the emergency department, a complete clinical and laboratory check including routine blood analysis, three blood cultures as well as cultures from any presumed infection focus, urinalysis and chest radiograph were performed. The Multinational Association of Supportive Care of Cancer (MASCC) risk-index score, which was originally developed to identify low-risk febrile neutropenic cancer patients 8), was calculated according to the criteria shown in Table 1, and was used as a tool for compensating the severity between two groups. Table 1. MASCC risk-index score Prognostic factor Burden of febrile neutropenia No or mild symptoms 5 Moderate symptoms 3 No hypotension (systolic blood pressure > 90 mmhg) 5 No chronic obstructive pulmonary disease 4 Solid tumor or hematologic malignancy with no previous fungal infection 4 No dehydration requiring parenteral fluids 3 Outpatient status 3 Age < 60 years 2 Weight Points attributed to the variable burden of illness are not cumulative. The maximum theoretical score is therefore 26 MASCC: Multinational Association of Supportive Care of Cancer

3 Shin Ahn, et al.: Effectiveness of a Specialized Emergency Department Unit for Cancer Patients in Management of Febrile Neutropenia / 349 Granulocyte-colony stimulating factor (G-CSF) was routinely administered until ANC reached 1,000 cells/mm 3 and empirical broad spectrum intravenous antibiotics were given until resolution of the events. In conformity with our institute s guideline which has base on Infectious Diseases Society of America (IDSA) s 2002 publication, patients were treated with cefepime or piperacillin/tazobactam plus ciprofloxacin or vancomycin depending on clinical severity, previous antibiotics susceptibility test and risk factors 3). Further therapy was adjusted on the basis of clinical response, culture results and sensitivity tests. The dependent variable of interest were the time interval between presentation to ED and first antibiotic administration, measured in hours, depicted as door-to-needle time, and the final outcome of each febrile neutropenic episode, designated as presence of adverse events or not. It was modified from the original study protocol of MASCC 8). Patients without adverse events were those whose fever subsided without serious medical complications, including persistent hypotension, respiratory failure, intensive care unit admission, prolonged decreased mental status, pulmonary edema, renal failure and other serious medical complications including death (Table 2). And the length of hospital stay, measured in days for those admitted, was calculated. Data gathered in retrospective manners from electronic medical records were reviewed and abstracted by a trained reviewer, who was blinded to the purpose of the study, using a structural data instrument. 4. Data analysis Univariate analyses using contingency tables and basic descriptive statistics were done. Statistical analysis was carried out using the χ 2 test for the nominal data, Mann-Whitney test for the medians of nonparameteric data and Student s t-test for the parametric data. All statistical analyses were performed with SPSS for Windows 11.0 (SPSS Inc, Chicago, USA). All reported p values are two-tailed, and p values < 0.05 were considered statistically significant. Results Between May 1, 2008, and August 31, 2008, 74 episodes of chemotherapy induced FN were documented. In 4 episodes, the patients were transferred from other facilities and prior antibiotics were administered. Thus the rest 70 episodes were included, and all were managed at the MER. Between May 1, 2009, and August 31, 2009, 70 episodes presented with FN, 3 being transferred from other facilities with prior antibiotics administration and were consequently excluded. Among the rest 67 episodes, 46 were managed at the CER and 21 were Table 2. Final outcome of febrile neutropenic episode Outcomes No adverse event Adverse event Definition Resolution of fever without development of serious medical complications. (Modification of initial antibiotic therapy allowed) Resolution of fever with at least one serious medical complication. 1. Persistent hypotension: systolic blood pressure less than 90 mmhg or a need for inotropic support to maintain blood pressure (Initial hypotension but normalized after hydration is not considered serious medical complication) 2. Respiratory failure: oxygen saturation less than 90% while breathing room air or a need for mechanical ventilation 3. Intensive care unit admission 4. Prolonged decreased mental state 5. Newly developed pulmonary edema on chest X-ray and requiring treatment 6. Renal failure requiring renal replacement therapy 7. Other complications judged serious and clinically significant by the investigator 8. Death Modified from the Multinational association of supportive care of cancer (MASCC) study

4 350 / 대한응급의학회지 : 제 21 권제 3 호 2010 managed at the MER. Regarding total 137 episodes, 46 were managed in the CER and 91 were managed in the MER. Median of patient ages were 55(16-91) years, and 42.3% were men. The numbers of underlying malignancies were 43(31.4%) in breast cancer, 25 (18.2%) in lymphoma, 14(10.2%) in lung cancer, 13 (9.5%) in stomach cancer, 9(6.6%) in sarcoma and 3 (2.2%) in leukemia. Thirty patients (21.9%) including colorectal, hepatobiliary, pancreas, urogenital cancer, multiple myeloma, and myelodysplastic syndrome etc. were classified as others. We analyzed the demographic and clinical characteristics of the febrile neutropenic episodes treated in the CER (n=46) vs. MER (n=91), (Table 3). All demographic and clinical variables between these two groups were similar, except for the patient ages. Ages were 52(16-78) years in the CER and 57 (18-91) years in the MER (p=0.035). Vital signs including systolic and diastolic blood pressure, respiratory rate and oxygen saturation showed insignificant differences (p=0.670, 0.227, 0.504, each). The numbers of absolute neutrophil count (ANC, cells/mm 3 ) were 85(0-660) and 106(0-890) Table 3. Characteristics of episode CER (n=46) MER (n=91) Age (yr)* 052 (16~78)0 57 (18~91) Male sex, N (%) 16 (34.8) 42 (46.2) Diagnosis, N (%) Breast cancer 18 (39.1) 25 (27.5) Lung cancer 05 (10.9) 09 (09.9) Lymphoma 07 (15.2) 18 (19.8) Stomach 04 (08.7) 09 (09.9) Sarcoma 03 (06.5) 06 (06.6) Leukemia 02 (04.3) 01 (01.1) Others 07 (15.2) 23 (25.2) Vital signs Systolic BP (mmhg) 109 (77~157) 109 (66~164) Diastolic BP (mmhg) 070 (43~119) 066 (46~105) RR (breaths/min) 20 (18~26) 20 (16~33) O 2 sat (%) 098 (93~100) 098 (85~100) Laboratory findings ANC (cells/mm 3 ) at presentation 85 (0~660) 106 (0~890)0 Serum creatinine (mg/dl).0.6 (0.4~1.1) 00.7 (0.3~5.3). AST (IU/L) 26 (5~643) 026 (11~210) ALT (IU/L) 28 (6~557) 21 (7~254) Serum platelet ( 10 3 /mm 3 ) 142 (6~444)0 105 (7~467)0 MASCC score 21, N (%) 33 (71.7)0 62 (68.1)0 Bacteremia on blood culture, N (%) 6 (13.0) 12 (13.2)0 CER: cancer emergency room, MER: main emergency room, BP: blood pressure, RR: respiratory rate, O 2 sat: oxygen saturation, ANC: absolute neutrophil count, AST: aspartate aminotransferase, ALT: alanine aminotransferase, MASCC: Multinational Association of Supportive Care of Cancer * p < 0.05 Table 4. Treatment related characteristics CER (n=46) MER (n=91) p-value Door-to-needle time (hrs) 02 (0.3~5.1).3.5 (0.9~6.9) Adverse events 12 (26.1) (46.2)0./ Admission, N (%) 37 (80.4) (81.3)0./ Length of hospital stay for those admitted (day) 04 (1~16)00.6 (1~51) CER: cancer emergency room, MER: main emergency room

5 Shin Ahn et al.: Effectiveness of a Specialized Emergency Department Unit for Cancer Patients in Management of Febrile Neutropenia / 351 in the CER and in the MER respectively (p=0.892). Differences in other laboratory findings including serum creatinine, aspartate aminotransferase, alanine aminotransferase and serum platelet counts were also insignificant (p=0.087, 0.386, 0.107, each). The proportion of episodes with MASCC score 21, which predicts low risk FN, was larger in the CER than MER, but statistically insignificant (71.7% vs. 68.1%, p=0.665). The rate of positive blood culture for bacteremia was similar between both groups (13.0% vs. 13.2%, p=0.981). The treatment related characteristics have also been reported and are shown in Table 4. The median door-to-needle time in patients managed in the CER was 2 hours ( ), significantly faster than 3.5 hours ( ) of the MER (p=0.000), (Fig. 1). Fig. 2. is a clustered box plot depicting the distribution of door-to-needle time in each group, according to the MASCC score classification. In the CER, the first dose of antibiotics were administered faster in the high risk febrile neutropenic episode, but in the MER difference in door-to-needle time was not shown among different risk groups. Significant differences in the final outcome between two groups Fig. 1. Box plot demonstrating the distribution of the length of antibiotic delivery (door-to-needle) times among episodes treated in the cancer emergency room (CER) compared with the episodes treated in the main emergency room (MER). The median door-toneedle times were 2 hours ( ) in the CER and 3.5 hours ( ) in the MER (p<0.01) Fig. 2. Clustered box plot demonstrating the distribution of the length of antibiotic delivery (door-to-needle) times among the episodes treated in the cancer emergency room (CER) compared with those episodes treated in the main emergency room (MER) according to the different risk groups (MASCC index score). In the CER, the first dose of antibiotics were administered faster in the high risk febrile neutropenic group, but in the MER, difference in doorto-needle time was not shown among different risk groups MASCC: Multinational Association of Supportive Care of Cancer Table 5. Subgroup analysis of treatment related characteristics in 2009 CER (n=46) MER (n=21) p-value Door-to-needle time (hrs).2 (0.3~5.1).3.5 (1.4~5.0) Adverse events 12 (26.1)000./ 14 (66.7)0./ Admission, N (%) 37 (80.4)000./ 19 (90.5)0./ Length of hospital stay for those admitted (day).4 (1~16)00.7 (1~51) CER: cancer emergency room, MER: main emergency room

6 352 / 대한응급의학회지 : 제 21 권제 3 호 2010 were found. Twelve episodes (26.1%) in the CER and 42(46.2%) episodes in the MER had adverse events (p=0.023). Differences in admission rate and duration of admission are also depicted. Admission rate in the CER and the MER were alike (80.4% vs. 81.3%, p=0.901), but the median length of hospital stay for those managed initially in the CER was 4 days (1-16), significantly shorter than that of 6 days (1-51) in the MER (p=0.034)(table 4). Sub-population analysis of 70 episodes between May 1, 2009, and August 31, 2009 were also performed. The median door-to-needle time in the CER was 2 hours ( ), still faster than that of 3.5 hours ( ) in the MER (p=0.001). Twelve (26.1%) episodes had adverse events in the CER and 14 (66.7%) in the MER (p=0.002). Admission rate in the CER and the MER showed insignificant difference (80.4% and 90.5%, p=0.500). The median length of hospital stay for those managed initially in the CER was 4 days (1-16), still significantly shorter than that of 7 days (1-51) in the MER (p=0.009) (Table 5). Discussion With increasing incidence of cancer in the general population and widespread use of cancer therapeutic agents relying on the outpatient treatments, ED physicians are increasingly encountering patients who present with diverse toxicities that are direct effects of chemotherapy 10). Almost all chemotherapeutic agents, as a single-agent therapy or a part of multidrug regimens, are capable of inducing neutropenia to various degrees. It is well known that the rapid administration of empirical antibiotics at the onset of fever before laboratory confirmation of infection is crucial, because the progression of infection in neutropenic patients can be rapid owing to the impaired host defense system, and because such patients with early bacterial infections cannot be reliably distinguished from non-infected patients at presentation 3). Early studies documented up to 70% mortality if initiation of antibiotics was delayed even more than a few hours 11). In May 2009, for the purpose of prompt and pertinent management of oncologic emergencies, the Asan Medical Center established an ED unit for cancer patients named CER, which is separated from the preexisting treatment area in ED. It is designed to segregate the cancer patients from the heterogeneous patient groups in ED, owing to their susceptibility to infections and their unique problems regarding malignancy and its treatment related complications. To the best of our knowledge, ED units separated and specialized for oncologic emergency management doesn t exist elsewhere. An institute in Spain runs the oncology acute toxicity unit (OATU) for improving the management of chemotherapy toxicity, but it is an outpatient facility, which is different from ours based on ED 12). Quality of care measurements and various performance indicators are developed in the health care problems or diseases with high volume, high morbidity and mortality 13). Among various indicators, antibiotic timing is well known and widely accepted. Multiple studies have reported associations between antibiotic timing and survival in various diseases 14-18). In this context, we chose the time to first antibiotic administration in FN as a quality of care measurement tool, which was never attempted in other studies. We observed statistically significant and clinically important associations between treatment area in ED for FN and time to first antibiotic administration. Clinical outcomes showed favorable results, and duration of admission were decreased for those managed in the CER. We believe that this relationship exists because more rapid antibiotic delivery in the CER may hasten the establishment of clinical stability, and accompanied by specialized and organized sequential care, resulted in more favorable outcomes and thus earlier discharges. Similar result was shown in the study of Lin et al. 19). In their study, delay of active antimicrobial therapy showed an increase in mortality for patients with severe neutropenia. In the study by Pines 20), factors associated with antibiotic delay were classified as presentation-level factors, patient-level factors, and system-level factors. Presentation-level factors include atypical symptoms, and patient-level factors include demographics and comorbid conditions that predispose patients to atypical presentations. Systematic factors include ED crowding, extended waiting times for evaluation, diagnosis and treatment and lack of organized

7 Shin Ahn et al.: Effectiveness of a Specialized Emergency Department Unit for Cancer Patients in Management of Febrile Neutropenia / 353 sequential care. It is well known that medical units dedicated to special subject can improve quality of care, including time to treatment such as antibiotics delivery 21). The CER can overcome the systemic factors by practicing based on organized management protocols specialized for oncologic emergencies. And the fixed maximal number of 18 patients in the CER, which leads this treatment area devoid of crowding, can also play a role in improving systemic factors. Considering the distribution of door-to-needle times according to the different risk groups, relevant and faster antibiotic administration was achieved in high risk groups compared with low risk groups in the CER. But in the MER, there showed no difference in the door-to-needle times among different risk groups. Not only earlier antibiotics administration, but also making a difference in compliance with the severity was shown in the CER. Owing to the location of the CER build on the sixth floor, which preclude the critical patients requiring immediate resuscitation from going upstairs, patients in a profound shock, requiring cardiopulmonary resuscitation or immediate advanced airway management are not suitable for management in the CER. One may assume that the difference in the clinical outcome may result from these factors, which might have caused selection bias in the study. But the MASCC risk-index score showed insignificant differences between both treatment areas, and other finding such as vital signs including blood pressure, and laboratory findings including blood culture results were not different significantly. It cannot be generalized that more favorable outcome found in the CER was due to earlier antibiotics administration solely. These data must be interpreted within the context of the study design. Retrospective medical record reviews were included in the study design and this might be inherently subject to selection bias. And the association between our measured door-to-needle time, outcomes of each FN episodes and length of hospital admission may be subject to unmeasured confounding factors, such as unmeasured pre-hospital parameters including the duration of fever before ED visit, or in-hospital processes of care, such as changing antibiotic regimen or switching parenteral to oral therapy, etc. Conclusion To the best of our knowledge, this study was the first report regarding the ED cancer unit, and relationship between the door-to-needle time of antibiotic administration and its outcome in febrile neutropenic episode. Establishing a unit for specialized management of oncologic emergency in ED can not be generalized, depending on the institute s size, manpower, economic status and treated patients pool. But, we found rapid delivery of antibiotics for FN in specialized ED unit for oncologic emergencies and its relationship with favorable outcomes and decreasing the length of hospital admission. Given the increasing incidence of cancer and various toxicities related to its treatment regimens, there is substantial interest in specialized management unit for oncologic emergencies in ED. This study was limited to the febrile neutropenic episodes among various oncologic emergencies. Expanding subjects to other entities are planned. REFERENCES 01. Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 2006;106: Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Clin Infect Dis 2005;40 suppl 4:S Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002;34: Hughes WT, Armstrong D, Bodey GP, Brown AE, Edwards JE, Feld R, et al guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis 1997;25: de Souza Viana L, Serufo JC, da Costa Rocha MO, Costa RN, Duarte RC. Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients. Support Care Cancer 2008;16: Gayol Mdel C, Font A, Casas I, Estrada O, Dominguez MJ, Pedro-Botet ML. Usefulness of the MASCC scale in

8 354 / 대한응급의학회지 : 제 21 권제 3 호 2010 the management of neutropenic fever induced by chemotherapy in patients with solid neoplasm. Med Clin (Barc) 2009;133: Innes H, Lim SL, Hall A, Chan SY, Bhalla N, Marshall E. Management of febrile neutropenia in solid tumours and lymphomas using the Multinational Association for Supportive Care in Cancer (MASCC) risk index: feasibility and safety in routine clinical practice. Support Care Cancer 2008;16: Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, et al. The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000;18: Corapcioglu F, Sarper N, Zengin E. Monotherapy with piperacillin/tazobactam versus cefepime as empirical therapy for febrile neutropenia in pediatric cancer patients: a randomized comparison. Pediatr Hematol Oncol 2006;23: Adelberg DE, Bishop MR. Emergencies related to cancer chemotherapy and hematopoietic stem cell transplantation. Emerg Med Clin North Am 2009;27: Schimpff S, Satterlee W, Young VM, Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med 1971;284: Majem M, Galan M, Perez FJ, Munoz M, Chicote S, Soler G, et al. The oncology acute toxicity unit (OATU): an outpatient facility for improving the management of chemotherapy toxicity. Clin Transl Oncol 2007;9: Mainz J. Developing evidence-based clinical indicators: a state of the art methods primer. Int J Qual Health Care 2003;15 Suppl 1:i Proulx N, Frechette D, Toye B, Chan J, Kravcik S. Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis. QJM 2005;98: Lepur D, Barsic B. Community-acquired bacterial meningitis in adults: antibiotic timing in disease course and outcome. Infection 2007;35: Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34: Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med 2004;164: Battleman DS, Callahan M, Thaler HT. Rapid antibiotic delivery and appropriate antibiotic selection reduce length of hospital stay of patients with community-acquired pneumonia: link between quality of care and resource utilization. Arch Intern Med 2002;162: Lin MY, Weinstein RA, Hota B. Delay of active antimicrobial therapy and mortality among patients with bacteremia: impact of severe neutropenia. Antimicrob Agents Chemother 2008;52: Pines JM. Timing of antibiotics for acute, severe infections. Emerg Med Clin North Am 2008;26: Beckett DJ, Raby E, Pal S, Jamdar R, Selby C. Improvement in time to treatment following establishment of a dedicated medical admissions unit. Emerg Med J 2009;26: