TY - JOUR
AU - Bombassaro, Anne Mari
AB - Abstract Objective The purpose of this study was to describe antimicrobial utilization, consumption, indications and microbial resistance in a medical-surgical-trauma intensive care unit (ICU) of a teaching hospital to identify potential targets for antimicrobial stewardship. Methods This was a 30-day prospective observational study enrolling adults admitted to the ICU for at least 24 h and having received antimicrobial therapy. Primary endpoints included utilization as percentage use of antimicrobials by class and agent, consumption measured as days of therapy per 1000 patient days (DOT/1000PD), indications for use and prescriber. Secondary endpoints included reasons for modifications to therapy and microbial resistance. Key findings Eighty-three patients were screened and 61 enrolled, receiving 133 courses of antimicrobial therapy, mainly intravenously and prescribed by ICU staff. The most frequently prescribed agents were piperacillin/tazobactam (20%), cefazolin (17%) and vancomycin (13%). The indications for therapy were empirical (50%), directed (27%) and prophylactic (23%). Overall consumption was 1368.54 DOT/1000PD and was mainly attributed to empirical therapy (734.25). Prolonged durations were noted for carbapenems and for surgical prophylaxis. There were 86 therapy modifications involving indication (36), efficacy (25), safety (18) and route (7). Suboptimal or excessive dosing were common contributors to efficacy and safety modifications, respectively. Infections due to microorganisms with notable resistance included methicillin-resistant Staphylococcus aureus (5), Pseudomonas aeruginosa (1) and Streptococcus pneumoniae (1). Conclusions Antimicrobial utilization and consumption based on DOT/1000PD were prospectively determined providing a comparator for other ICUs. Potential targets identified for antimicrobial stewardship initiatives include empirical therapy, treatment duration, dosing and route. antibiotic, antifungal, antimicrobial, days of therapy, intensive care unit, stewardship Introduction Antimicrobial resistance is increasing worldwide and threatening the effectiveness of antibiotic therapy.[1] The intensive care unit (ICU) in particular may be a ‘hot zone’ for the emergence and spread of microbial resistance due to invasive procedures and high antibiotic usage.[2] Rates of nosocomial infections range from 5 to 30% in ICUs, leading to antimicrobial consumption approximately 10 times greater than that of other wards.[3] Antimicrobial stewardship is recognized as a critical component of ICU care. The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America recently published guidelines for developing institutional programs for antimicrobial stewardship.[4] These guidelines define antimicrobial stewardship as an activity that includes the appropriate selection, dose, route and duration of antimicrobial therapy for the purpose of optimizing clinical outcomes while minimizing the unintended consequences of use such as toxicity, superinfection and the emergence of resistance.[4] An awareness of antimicrobial prescribing, infections and pathogens is key to guiding antimicrobial stewardship initiatives within individual ICUs and provides benchmarking opportunities for the critical care community worldwide. The IDSA stewardship guidelines recommend using the World Health Organization defined daily dose per 1000 patient days (DDD/1000PD) as the measurement unit for antimicrobials.[4] An alternative measure of consumption using days of therapy per 1000 patient days (DOT/1000PD) has been evaluated.[5,6] The preferred measurement approach remains unresolved.[5–8] Suggested advantages of the DOT methodology are that it is not influenced by changes in the recommended DDD, or discrepancies between the DDD and the preferred daily dose and by dose-adjustment in renal insufficiency.[5,8] The latter aspect is of particular relevance in a critical care population. The objectives of this study were to describe antimicrobial utilization, consumption using the DOT methodology, indications for therapy and microbial resistance in a tertiary care ICU to identify targets to be considered for stewardship initiatives. Methods This was a prospective observational study in a 30-bed adult medical/surgical/trauma ICU of an 846-bed tertiary care teaching hospital. Approval for the study was obtained from the Office of Research Ethics at the University of Western Ontario, London, ON, Canada (Lawson Health Research Institute, January 2010). All patients admitted to the ICU over the 30-day period, between 8 February and 9 March 2010, were screened for inclusion. Exclusion criteria were admission to the ICU with a stay of less than 24 h or no antimicrobial therapy during the stay. Direct patient care in the ICU was provided by physicians and surgeons who were unaware that the study was taking place. During the study period there were no institution- or unit-specific antimicrobial guidelines other than those for surgical prophylaxis. Two ICU pharmacists, who were involved in the design of the study, delivered pharmaceutical care according to their routine practices. Direct patient care time during the study period was scheduled in accordance with existing departmental guidelines (approximately 4 h/day per pharmacist from Monday to Friday). The amount of pharmacist time in the ICU was consistent with usual pharmacy scheduling practices and was not increased because of the study initiative. Daily chart review and data extraction were performed by a designated study pharmacist, familiar with ICU practice but not involved in the daily care of patients. Included patients were followed until the first of four endpoints occurred: 30-day stay in the ICU, discontinuation of antimicrobial therapy, transfer out of the unit or death during the stay. Patient information was recorded on manually completed data forms. This included patient demographics, antimicrobial regimens (agents, doses and routes), indications for therapy, antimicrobial start/stop dates and times, positive culture and susceptibility results, modifications to therapy and the prescriber. Length of stay was recorded for all patients admitted to the ICU during the study period. Endpoints and definitions Primary endpoints included the percentage use of antimicrobials by class and agent, indications for use, antimicrobial consumption, routes of administration and prescribers. Antimicrobials encompassed systemic antibiotics or antifungals prescribed for the purpose of preventing or treating an infection. Percentage use was defined as the number of treatment courses of a particular class and agent divided by the total number of treatment courses. A treatment course referred to any antimicrobial prescribed regardless of the duration of administration. Restarting the same agent up to 48 h after discontinuation was defined a priori as the same treatment course, whereas restarting the same antimicrobial beyond 48 h of discontinuation was considered a new treatment course. Prescribers of antimicrobials included the critical care staff as well as consulting services such as surgery, medicine and infectious diseases. Indications for use were categorized as directed, empirical or prophylaxis. Directed therapy was defined as treatment of an infection with documented pathogen(s) (positive culture). Empirical therapy was defined as treatment of an infection in the absence of a defined pathogen or positive culture. Prophylaxis referred to the use of an antimicrobial in the absence of a known or suspected infection or pathogen. The indication for use was accepted as documented in the chart. Antimicrobial consumption during the study period was expressed as DOT/1000PD, as described by Polk and colleagues.[5] One day of therapy represented the administration of a single agent on a given day regardless of the number of doses administered or dosage strength.[5] Days of therapy were confirmed by verifying dose administration on the medication record on a daily basis. For study purposes a day was standardized as a 24 h period starting at 0700 h. The length of stay for all patients admitted to the ICU during the study period was summed to determine the total number of patient days. Secondary endpoints included the number of and reasons for modifications to the antimicrobial regimens, the prescriber making the change and the median time to modification after reporting of a positive culture (preliminary and/or final). The reasons for modifications were grouped into four categories including indication, efficacy, safety and intravenous to enteral interchange. Modifications related to indication included broadening the spectrum of coverage, streamlining (narrowing spectrum, or eliminating duplicate therapy) and discontinuation, based on the clinical status of the patient and/or culture results. Efficacy was defined as a change to a regimen deemed more effective or a dose increase according to the clinical scenario or culture results. Safety referred to a change in therapy due to an adverse event or the presence of precautions/contraindications such as interactions or excess doses (milligram amount or frequency). Patients admitted to the ICU were routinely screened for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) colonization according to pre-existing policy. The percentage of included patients with MRSA colonization (nasal/rectal) and VRE colonization (rectal) was identified. Microbiological data were collected only for patients receiving antimicrobial therapy directed to documented pathogens. Statistical analysis A descriptive analysis of endpoints was performed. Normally and non-normally distributed data were expressed as means and standard deviation (SD) or medians with interquartile range (IQR), respectively. Post hoc analysis was performed on two select secondary endpoints. The Wilcoxon test was used to analyse non-parametric data to compare time to modification after a culture result. A Chi-square test was used to analyse changes in prevalence of MRSA and VRE colonization during the study period. Data were stored using Excel (Microsoft Corporation, Redmond, WA, USA) and analysed using JMP software, version 9.0.2 (SAS, Cary, NC, USA). A significance level of 0.05 was used. Results Eighty-three patients were admitted to the ICU and screened for study eligibility. Sixty-one patients (73%) met the inclusion criteria. Of the 22 excluded patients, three died within 24 h, four were transferred out of the unit within 24 h and 15 did not receive antimicrobials. Demographic characteristics are summarized in Table 1.[9] The numbers of admissions to the ICU for medical and surgical-trauma reasons were similar: 52 and 48%, respectively. Table 1 Patient characteristics (n = 61) Age (years), mean±SD 61±18.3 Male, n (%) 37 (61) MODS[9] at baseline, median (IQR) 5 (4–7) Location prior to ICU admission, n (%) Emergency department 23 (38) Operating room 19 (31) Inpatient ward 14 (23) Peripheral hospital 5 (8) Reason for ICU admission, n (%) Surgical 18 (30) Medical Non-infection-related 19 (31) Infection-related 13 (21) Trauma 11 (18) Length of stay (days), median (IQR) 5 (3.1–12.3) VRE colonized at baseline, n (%)a 6 (10) MRSA colonized at baseline, n (%)b 3 (5) Age (years), mean±SD 61±18.3 Male, n (%) 37 (61) MODS[9] at baseline, median (IQR) 5 (4–7) Location prior to ICU admission, n (%) Emergency department 23 (38) Operating room 19 (31) Inpatient ward 14 (23) Peripheral hospital 5 (8) Reason for ICU admission, n (%) Surgical 18 (30) Medical Non-infection-related 19 (31) Infection-related 13 (21) Trauma 11 (18) Length of stay (days), median (IQR) 5 (3.1–12.3) VRE colonized at baseline, n (%)a 6 (10) MRSA colonized at baseline, n (%)b 3 (5) a Two patients were not screened at baseline (n = 59). b One patient was not screened at baseline (n = 60). SD, standard deviation; MODS, multiple-organ dysfunction score; ICU, intensive care unit; IQR, interquartile range; VRE, vancomycin-resistant enterococcus; MRSA, methicillin-resistant Staphylococcus aureus. Open in new tab Table 1 Patient characteristics (n = 61) Age (years), mean±SD 61±18.3 Male, n (%) 37 (61) MODS[9] at baseline, median (IQR) 5 (4–7) Location prior to ICU admission, n (%) Emergency department 23 (38) Operating room 19 (31) Inpatient ward 14 (23) Peripheral hospital 5 (8) Reason for ICU admission, n (%) Surgical 18 (30) Medical Non-infection-related 19 (31) Infection-related 13 (21) Trauma 11 (18) Length of stay (days), median (IQR) 5 (3.1–12.3) VRE colonized at baseline, n (%)a 6 (10) MRSA colonized at baseline, n (%)b 3 (5) Age (years), mean±SD 61±18.3 Male, n (%) 37 (61) MODS[9] at baseline, median (IQR) 5 (4–7) Location prior to ICU admission, n (%) Emergency department 23 (38) Operating room 19 (31) Inpatient ward 14 (23) Peripheral hospital 5 (8) Reason for ICU admission, n (%) Surgical 18 (30) Medical Non-infection-related 19 (31) Infection-related 13 (21) Trauma 11 (18) Length of stay (days), median (IQR) 5 (3.1–12.3) VRE colonized at baseline, n (%)a 6 (10) MRSA colonized at baseline, n (%)b 3 (5) a Two patients were not screened at baseline (n = 59). b One patient was not screened at baseline (n = 60). SD, standard deviation; MODS, multiple-organ dysfunction score; ICU, intensive care unit; IQR, interquartile range; VRE, vancomycin-resistant enterococcus; MRSA, methicillin-resistant Staphylococcus aureus. Open in new tab Primary endpoints Sixty-one patients received a total of 133 courses of antimicrobial therapy. This figure includes a second antimicrobial course initiated at least 72 h after completing the first course in four patients. Antimicrobial courses were most commonly prescribed by ICU staff (95/133, 71%) followed by surgery (28/133, 21%), medicine (7/133, 5%), and infectious diseases (3/133, 2%). The majority of orders written by surgical staff (17/28, 61%) were for peri-operative prophylaxis. The 133 treatment courses encompassed 12 antimicrobial classes (Table 2) and 21 individual agents (Table 3). Antibiotics were prescribed in 125 courses (94%) and antifungals in only eight courses (6%). No patient received an antifungal without a concomitant antibiotic. The classes of antimicrobials that accounted for greater than 10% of treatment courses in descending order were cephalosporins, β-lactam/β-lactamase inhibitors, fluoroquinolones and glycopeptides (Table 2). Piperacillin/tazobactam was the most commonly prescribed agent followed by cefazolin and vancomycin (Table 3). Each of these agents accounted for greater than 10% of treatment courses. One-hundred and twenty of the 133 antimicrobial courses (90%) were initially administered intravenously and 13 (10%) enterally. Table 2 Antimicrobial use and consumption by class Class . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Cephalosporin 28 21.1 181.75 13.3 (4) First generation 22 16.5 130.86 9.6 Second generation 1 0.8 19.99 1.5 Third generation 5 3.8 30.90 2.2 β-Lactamase inhibitor 27 20.3 296.25 21.6 (1) Fluoroquinolone 19 14.3 179.93 13.1 (5) Glycopeptide 17 12.8 187.20 13.7 (3) Carbapenem 11 8.3 196.29 14.3 (2) Nitroimidazole 9 6.8 65.43 4.8 Antifungal 8 6.0 143.58 10.5 Miscellaneousc 7 5.3 63.61 4.7 Macrolide 5 3.7 36.35 2.7 Penicillin 2 1.5 18.17 1.3 Class . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Cephalosporin 28 21.1 181.75 13.3 (4) First generation 22 16.5 130.86 9.6 Second generation 1 0.8 19.99 1.5 Third generation 5 3.8 30.90 2.2 β-Lactamase inhibitor 27 20.3 296.25 21.6 (1) Fluoroquinolone 19 14.3 179.93 13.1 (5) Glycopeptide 17 12.8 187.20 13.7 (3) Carbapenem 11 8.3 196.29 14.3 (2) Nitroimidazole 9 6.8 65.43 4.8 Antifungal 8 6.0 143.58 10.5 Miscellaneousc 7 5.3 63.61 4.7 Macrolide 5 3.7 36.35 2.7 Penicillin 2 1.5 18.17 1.3 Where relevant, the ranking is given in parentheses. a Number of courses per class ×100 divided by total courses of therapy (133). b (DOT/1000PD per class ×100) divided by aggregate DOT/1000PD of all antimicrobials (1368.54). c Miscellaneous classes: monobactam, lincosamide and sulfamethoxazole/trimethoprim. DOT/1000PD, days of therapy per 1000 patient days; β-Lactamase inhibitor, β-lactam/β-lactamase inhibitor. Open in new tab Table 2 Antimicrobial use and consumption by class Class . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Cephalosporin 28 21.1 181.75 13.3 (4) First generation 22 16.5 130.86 9.6 Second generation 1 0.8 19.99 1.5 Third generation 5 3.8 30.90 2.2 β-Lactamase inhibitor 27 20.3 296.25 21.6 (1) Fluoroquinolone 19 14.3 179.93 13.1 (5) Glycopeptide 17 12.8 187.20 13.7 (3) Carbapenem 11 8.3 196.29 14.3 (2) Nitroimidazole 9 6.8 65.43 4.8 Antifungal 8 6.0 143.58 10.5 Miscellaneousc 7 5.3 63.61 4.7 Macrolide 5 3.7 36.35 2.7 Penicillin 2 1.5 18.17 1.3 Class . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Cephalosporin 28 21.1 181.75 13.3 (4) First generation 22 16.5 130.86 9.6 Second generation 1 0.8 19.99 1.5 Third generation 5 3.8 30.90 2.2 β-Lactamase inhibitor 27 20.3 296.25 21.6 (1) Fluoroquinolone 19 14.3 179.93 13.1 (5) Glycopeptide 17 12.8 187.20 13.7 (3) Carbapenem 11 8.3 196.29 14.3 (2) Nitroimidazole 9 6.8 65.43 4.8 Antifungal 8 6.0 143.58 10.5 Miscellaneousc 7 5.3 63.61 4.7 Macrolide 5 3.7 36.35 2.7 Penicillin 2 1.5 18.17 1.3 Where relevant, the ranking is given in parentheses. a Number of courses per class ×100 divided by total courses of therapy (133). b (DOT/1000PD per class ×100) divided by aggregate DOT/1000PD of all antimicrobials (1368.54). c Miscellaneous classes: monobactam, lincosamide and sulfamethoxazole/trimethoprim. DOT/1000PD, days of therapy per 1000 patient days; β-Lactamase inhibitor, β-lactam/β-lactamase inhibitor. Open in new tab Table 3 Antimicrobial use and consumption by agent Antimicrobial . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Piperacillin/tazobactam 27 20.3 296.25 21.6 (1) Cefazolin 22 16.5 130.86 9.6 (3) Vancomycin 17 12.8 187.20 13.7 (2) Ciprofloxacin 10 7.5 74.52 5.4 Levofloxacin 9 6.8 105.41 7.7 Metronidazole 9 6.8 65.43 4.8 Meropenem 6 4.5 69.06 5.0 Azithromycin 5 3.7 36.35 2.7 Fluconazole 5 3.7 112.68 8.2 (5) Imipenem 5 3.7 127.22 9.3 (4) Cefotaxime 4 3.0 23.63 1.8 SMX/TMP 4 3.0 32.71 2.4 Clindamycin 2 1.5 16.36 1.2 L-AMB 1 0.8 16.36 1.2 Aztreonam 1 0.8 14.54 1.0 Caspofungin 1 0.8 3.63 0.3 Ceftazidime 1 0.8 7.27 0.5 Cefuroxime 1 0.8 19.99 1.5 Cloxacillin 1 0.8 1.82 0.1 Penicillin G 1 0.8 16.36 1.2 Posaconazole 1 0.8 10.90 0.8 Antimicrobial . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Piperacillin/tazobactam 27 20.3 296.25 21.6 (1) Cefazolin 22 16.5 130.86 9.6 (3) Vancomycin 17 12.8 187.20 13.7 (2) Ciprofloxacin 10 7.5 74.52 5.4 Levofloxacin 9 6.8 105.41 7.7 Metronidazole 9 6.8 65.43 4.8 Meropenem 6 4.5 69.06 5.0 Azithromycin 5 3.7 36.35 2.7 Fluconazole 5 3.7 112.68 8.2 (5) Imipenem 5 3.7 127.22 9.3 (4) Cefotaxime 4 3.0 23.63 1.8 SMX/TMP 4 3.0 32.71 2.4 Clindamycin 2 1.5 16.36 1.2 L-AMB 1 0.8 16.36 1.2 Aztreonam 1 0.8 14.54 1.0 Caspofungin 1 0.8 3.63 0.3 Ceftazidime 1 0.8 7.27 0.5 Cefuroxime 1 0.8 19.99 1.5 Cloxacillin 1 0.8 1.82 0.1 Penicillin G 1 0.8 16.36 1.2 Posaconazole 1 0.8 10.90 0.8 Where relevant, the ranking is given in parentheses. a Number of courses per agent ×100 divided by total courses of therapy (133). b (DOT/1000PD per agent ×100) divided by aggregate DOT/1000PD of all antimicrobials (1368.54). DOT/1000PD, days of therapy per 1000 patient days; SMX/TMP, sulfamethoxazole/trimethoprim; L-AMB, liposomal amphotericin B. Open in new tab Table 3 Antimicrobial use and consumption by agent Antimicrobial . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Piperacillin/tazobactam 27 20.3 296.25 21.6 (1) Cefazolin 22 16.5 130.86 9.6 (3) Vancomycin 17 12.8 187.20 13.7 (2) Ciprofloxacin 10 7.5 74.52 5.4 Levofloxacin 9 6.8 105.41 7.7 Metronidazole 9 6.8 65.43 4.8 Meropenem 6 4.5 69.06 5.0 Azithromycin 5 3.7 36.35 2.7 Fluconazole 5 3.7 112.68 8.2 (5) Imipenem 5 3.7 127.22 9.3 (4) Cefotaxime 4 3.0 23.63 1.8 SMX/TMP 4 3.0 32.71 2.4 Clindamycin 2 1.5 16.36 1.2 L-AMB 1 0.8 16.36 1.2 Aztreonam 1 0.8 14.54 1.0 Caspofungin 1 0.8 3.63 0.3 Ceftazidime 1 0.8 7.27 0.5 Cefuroxime 1 0.8 19.99 1.5 Cloxacillin 1 0.8 1.82 0.1 Penicillin G 1 0.8 16.36 1.2 Posaconazole 1 0.8 10.90 0.8 Antimicrobial . Number of courses . % Usea . DOT/1000PD . % Consumptionb . Piperacillin/tazobactam 27 20.3 296.25 21.6 (1) Cefazolin 22 16.5 130.86 9.6 (3) Vancomycin 17 12.8 187.20 13.7 (2) Ciprofloxacin 10 7.5 74.52 5.4 Levofloxacin 9 6.8 105.41 7.7 Metronidazole 9 6.8 65.43 4.8 Meropenem 6 4.5 69.06 5.0 Azithromycin 5 3.7 36.35 2.7 Fluconazole 5 3.7 112.68 8.2 (5) Imipenem 5 3.7 127.22 9.3 (4) Cefotaxime 4 3.0 23.63 1.8 SMX/TMP 4 3.0 32.71 2.4 Clindamycin 2 1.5 16.36 1.2 L-AMB 1 0.8 16.36 1.2 Aztreonam 1 0.8 14.54 1.0 Caspofungin 1 0.8 3.63 0.3 Ceftazidime 1 0.8 7.27 0.5 Cefuroxime 1 0.8 19.99 1.5 Cloxacillin 1 0.8 1.82 0.1 Penicillin G 1 0.8 16.36 1.2 Posaconazole 1 0.8 10.90 0.8 Where relevant, the ranking is given in parentheses. a Number of courses per agent ×100 divided by total courses of therapy (133). b (DOT/1000PD per agent ×100) divided by aggregate DOT/1000PD of all antimicrobials (1368.54). DOT/1000PD, days of therapy per 1000 patient days; SMX/TMP, sulfamethoxazole/trimethoprim; L-AMB, liposomal amphotericin B. Open in new tab Of the 133 antimicrobial courses, 67 (50%) were empirical, 36 (27%) were directed and 30 (23%) were prophylactic. Empirical therapy was administered for a median of 4 days (IQR, 2–8 days). Nine of the 67 (13%) empirical courses exceeded 10 days in duration. Of note, two of the nine courses (imipenem with fluconazole) were administered throughout the 30-day study period for an intra-abdominal focus in the absence of source control. The 36 courses of directed antimicrobial therapy were administered for a mean of 6.9±3.7 days. These courses were prescribed for positive cultures in 23 patients and involved 33 sites of infection: lung (10), urinary tract (nine), blood (six), intra-abdominal (four, with Clostridium difficile diarrhoea in two) and skin and soft tissue (four). Three individual antimicrobial courses were directed to more than one concurrent site of infection. Conversely, combination courses of antimicrobials were directed to five infection sites, including the lung (three), urinary tract (one) and intra-abdominal (C. difficile diarrhoea) (one). Cefazolin was prescribed in 17 of the 30 (57%) prophylactic courses. The duration of prophylaxis with cefazolin exceeded a 24 h period in six out of 17 (35%) courses and involved surgeries other than cardiothoracic. These six cefazolin courses were administered for a mean of 3.67±0.52 days. The 133 antimicrobial courses resulted in 753 days of therapy (mean 5.66±4.74 days). During the study period there were 550 ICU patient days. Antimicrobial consumption described as DOT/1000PD was 1368.54 with 1224.96 (90%) of this attributed to antibiotic classes. Antifungals contributed minimally (143.58 or 10%) to overall consumption. The three largest class contributors, in descending order, were β-lactam/ β-lactamase inhibitors, carbapenems and glycopeptides (Table 2). In terms of individual agents, piperacillin/tazobactam followed by vancomycin and cefazolin were the three largest contributors to consumption (Table 3). Percentage consumption as expressed by DOT/1000PD paralleled percentage use for the majority of antimicrobial classes and individual agents. Exceptions to this trend included the carbapenem class, for which a higher percentage of consumption compared to percentage use was most evident (14.3 versus 8.3%) followed by the antifungal class (10.5 versus 6%) (Table 2). This was supported by trends for individual agents within these classes: imipenem (9.3 versus 3.7%) and fluconazole (8.2 versus 3.7%) (Table 3). Conversely, the first-generation cephalosporin class (cefazolin) demonstrated lower percentage consumption than percentage use (9.6 versus 16.5%) (Tables 2 and 3). Antimicrobial consumption described as DOT/1000PD according to indication for use was greatest for empirical (734.25; 54%) followed by directed (454.36; 33%) and prophylactic indications (179.93; 13%) (Figure 1). Antibiotic versus antifungal consumption predominated for each of these indications (Figure 1). Figure 1 Open in new tabDownload slide Antimicrobial consumption by indication. DOT/1000PD, days of therapy per 1000 patient days. Secondary endpoints Eighty-six modifications were made to the 133 antimicrobial treatment courses (in 61 patients), resulting in 0.65 modifications per course or 1.41 modifications per patient. The ICU staff and the infectious diseases consult service initiated 66 (77%) and 19 (22%) of the 86 modifications, respectively. The median time from the report of a culture result (preliminary and/or final) to modification of a regimen was 2.77 h (IQR, 1.71–25.74 h). The median time to modification was 2.32 h (IQR, 0.88–7.64 h) for infectious disease prescribers compared to 5.42 h (IQR, 2.77–27.88 h) for ICU prescribers (P = 0.08). The most frequent reason for regimen modification was indication (36/86, 42%). Discontinuation, streamlining and broadening of therapy accounted for 20, 14 and two of these modifications, respectively. Of the 20 discontinuations, 19 were based on clinical status or negative culture. The second most frequent reason for regimen modification was efficacy (25/86, 29%), which was related to suboptimal dosing in 20/25, mainly of piperacillin/tazobactam and vancomycin. Safety-related concerns accounted for 18/86 (21%) of modifications. Excessive dosing was the main contributor for 14 out of 18, with vancomycin and imipenem being most commonly implicated. Intravenous to enteral interchange was responsible for a minimal number of regimen modifications (seven out of 120 treatment courses, 5.8%). The prevalence of MRSA and VRE colonization was three in 60 (5%) and six in 59 (10%), respectively, of patients screened on admission to the ICU (Table 1). This increased, with subsequent surveillance over the study period, to five out of 61 (8%) for MRSA and nine out of 61 (15%) for VRE. The observed increases were not statistically significant (P = 0.48 and 0.45 respectively). Twenty-three patients received 36 directed courses of therapy for infections involving 43 unique patient isolates (Table 4). The frequencies of Gram-positive (19/43) and Gram-negative bacteria (19/43) were identical (Table 4). Table 4 Microorganisms in culture-positive infected patients (n = 23) Microorganism . Isolates, n = 43 . Gram-positive 19 (44%) Staphylococcus aureus 7 MRSA 5 Staphylococcus epidermidis 3 Enterococcus species 3 Streptococcus pyogenes 1 Streptococcus pneumoniae 1 Othera 4 Gram-negative 19 (44%) Escherichia coli 7 Pseudomonas species 4 Klebsiella species 3 Enterobacter species 2 Stenotrophomonas maltophilia 2 Serratia marcescens 1 Anaerobes 3 (7%) Clostridium difficile 2 Clostridia species 1 Fungi 2 (5%) Yeast/Candida speciesb 2 Microorganism . Isolates, n = 43 . Gram-positive 19 (44%) Staphylococcus aureus 7 MRSA 5 Staphylococcus epidermidis 3 Enterococcus species 3 Streptococcus pyogenes 1 Streptococcus pneumoniae 1 Othera 4 Gram-negative 19 (44%) Escherichia coli 7 Pseudomonas species 4 Klebsiella species 3 Enterobacter species 2 Stenotrophomonas maltophilia 2 Serratia marcescens 1 Anaerobes 3 (7%) Clostridium difficile 2 Clostridia species 1 Fungi 2 (5%) Yeast/Candida speciesb 2 a Coagulase-negative Staphylococci (two) and diphtheroids (two) as part of polymicrobial cultures involving skin/soft-tissue infections. b Part of polymicrobial cultures involving urinary (one) and respiratory (one) tracts. MRSA, methicillin-resistant S. aureus. Open in new tab Table 4 Microorganisms in culture-positive infected patients (n = 23) Microorganism . Isolates, n = 43 . Gram-positive 19 (44%) Staphylococcus aureus 7 MRSA 5 Staphylococcus epidermidis 3 Enterococcus species 3 Streptococcus pyogenes 1 Streptococcus pneumoniae 1 Othera 4 Gram-negative 19 (44%) Escherichia coli 7 Pseudomonas species 4 Klebsiella species 3 Enterobacter species 2 Stenotrophomonas maltophilia 2 Serratia marcescens 1 Anaerobes 3 (7%) Clostridium difficile 2 Clostridia species 1 Fungi 2 (5%) Yeast/Candida speciesb 2 Microorganism . Isolates, n = 43 . Gram-positive 19 (44%) Staphylococcus aureus 7 MRSA 5 Staphylococcus epidermidis 3 Enterococcus species 3 Streptococcus pyogenes 1 Streptococcus pneumoniae 1 Othera 4 Gram-negative 19 (44%) Escherichia coli 7 Pseudomonas species 4 Klebsiella species 3 Enterobacter species 2 Stenotrophomonas maltophilia 2 Serratia marcescens 1 Anaerobes 3 (7%) Clostridium difficile 2 Clostridia species 1 Fungi 2 (5%) Yeast/Candida speciesb 2 a Coagulase-negative Staphylococci (two) and diphtheroids (two) as part of polymicrobial cultures involving skin/soft-tissue infections. b Part of polymicrobial cultures involving urinary (one) and respiratory (one) tracts. MRSA, methicillin-resistant S. aureus. Open in new tab Infections due to microorganisms that exhibited notable resistance, other than MRSA, were as follows: a urinary tract infection due to multidrug-resistant Pseudomonas aeruginosa (as defined by 3-class resistance[10]) and a pneumonia due to Streptococcus pneumoniae with penicillin resistance and intermediate susceptibility to cefotaxime by meningeal interpretation. There were no infections due to extended-spectrum β-lactamase or carbapenamase-producing Enterobacteriaceae, VRE, or vancomycin-intermediate or -resistant S. aureus. Reported minimum inhibitory concentrations of vancomycin for all MRSA isolates were ≤1 mg/L (Vitek 2 System/Biomerieux). Discussion This prospective, observational study of antimicrobial use within a single ICU identified specific targets for the advancement of stewardship. Furthermore, it provides baseline data against which to measure the success of future interventions and benchmarking data for similar ICUs. The majority of antimicrobials were prescribed for empirical indications, with the most commonly prescribed agent being piperacillin/tazobactam. Unexpectedly, consumption of carbapenems was higher than their percentage use and prolonged durations were noted for surgical prophylaxis. A strength of this study was the prospective design which ensured complete data collection and verification of daily dose administration to accurately determine antibiotic consumption and prescribing patterns. Unique to the design of this study was the determination of antimicrobial consumption using DOT/1000PD in a strictly ICU setting. Limitations of this study include its single-centre design and short observation period. Since medical and surgical residents rotate through the ICU on a monthly basis, the study reflects the prescribing patterns of a specific group. Due to the observational design of the study and desire to preserve prescriber blinding to data collection, no attempt was made to adjudicate or verify the documented indications for therapy or the appropriateness of therapy modifications. Additionally, clinical pharmacists in the ICU participated in the development of the study design which may have increased their attention to antimicrobial stewardship. During the 30-day study period 73% of patients admitted to the ICU for at least 24 h received antimicrobials. This figure closely approximates the 71% reported in a point prevalence study conducted in 2007 of participating ICUs from 75 countries.[11] Of the 133 antimicrobial treatment courses administered in the current study, antibiotics accounted for the majority (94%) compared to antifungals (6%). The antibiotic classes prescribed in greater than 10% of courses were cephalosporins, β-lactam/β-lactamase inhibitors, fluoroquinolones and glycopeptides. This utilization pattern is similar to that described in a point prevalence survey of Canadian critical care units during which cephalosporins were most commonly prescribed (15.4%), followed by fluoroquinolones (13.3%), penicillins (10.9%) and vancomycin (9.4%).[12] Aminoglycosides were infrequently used (2.4%) in the point prevalence survey[12] and were not prescribed at all in this study. The preference of fluoroquinolones over aminoglycosides identifies a trend towards the use of less toxic antimicrobial classes. The calculated value of 1368.54 DOT/1000PD in this study exceeds the mean of 855 DOT/1000PD reported in a study of university teaching hospitals in the USA that captured aggregate, rather than ICU-specific, data using electronic claims.[6] These methodological differences make comparison of study results problematic. However, greater use of antimicrobials in an ICU versus an aggregate setting (ICU, medical and surgical wards) has been previously described using the traditional DDD/1000PD methodology (1517.7 versus 718.5, respectively) at a university hospital in France.[7] Percentage use and consumption were found to parallel each other for the majority of antimicrobials. Deviations between these two measureables assisted in identifying targets for antimicrobial stewardship. The percentage use of first-generation cephalosporins/cefazolin (16.5%) was notably higher than the corresponding percentage consumption (9.6%). This difference is attribuTable o the fact that although cefazolin was used frequently it was mainly prescribed for short-course peri-operative prophylaxis. Of note, 35% of peri-operative prophylaxis with cefazolin exceeded the maximum 24 h duration recommended by institutional and published guidelines[13] for procedures other than cardiothoracic. In comparison, carbapenems were used infrequently (8.3%), yet contributed disproportionately to consumption (14.3%). Their prolonged use in patients with inadequate intra-abdominal source control contributed to this difference. Concurrent prescribing of the antifungal class (mainly fluconazole) in such scenarios also explains its higher consumption relative to frequency of use. The above observations suggest that stewardship initiatives should direct educational efforts to shortening durations of antimicrobial exposure, particularly of cefazolin for surgical prophylaxis and of carbapenems and fluconazole in the management of intra-abdominal infections. Empirical therapy was the most common indication for prescribing, accounting for 50% of antimicrobial courses and for 54% of consumption. A prospective evaluation in a surgical and trauma ICU found that of 312 patients receiving empirical therapy only 25.6% were found to have an infection.[14] The empirical antibiotic group had a greater number of total antibiotic days, was more likely to develop a confirmed infection, and had more resistant organisms and a higher ICU mortality rate.[14] These results highlight the relevance of the observation that empirical therapy contributed substantially to antimicrobial consumption in this study. Therefore stewardship efforts should include a review of the current approach to empirical prescribing. Parenteral to enteral conversion is recognized as an important stewardship activity.[4] In this study 90% of initial treatment courses were given parenterally and only 5.8% of these were transitioned to the enteral route. Although the study was not designed to assess the eligibility for and subsequent conversion to enteral administration, a re-evaluation of current practice regarding this stewardship activity is warranted. The majority of modifications made to antimicrobial therapy were indication-related and resulted in discontinuation or streamlining of therapy. Changes that were made for efficacy and safety reasons frequently involved dose modification, particularly for piperacillin/tazobactam and vancomycin. Educational efforts addressing pharmacokinetics and pharmacodynamics of piperacillin/tazobactam for Gram-negative pathogens and vancomycin for S. aureus infections will promote stewardship through dose optimization to maximize efficacy and minimize risks associated with suboptimal dosing.[15,16] The collection of microbiological data in the current analysis was restricted to patients treated for infection with documented microorganisms, with the exception of MRSA and VRE colonization status. Microbiological data were not collected for patients deemed by their physicians to be uninfected. S. aureus and Escherichia coli were the most commonly isolated Gram-positive and Gram-negative pathogens, respectively. This is consistent with the pattern of organisms observed in culture-positive infected patients from the North American sites enrolled in the international ICU point prevalence study and in the Canadian National Intensive Care Unit (CAN-ICU) analysis.[1,11] The observed 5% prevalence of MRSA colonization upon ICU admission is comparable to the 4% prevalence reported by other Canadian centres and at the low end of ranges reported by French (3.7–20%) and US ICUs (5–21%).[17–19]C. difficile diarrhoea occurred in 2/61 (3.3%) patients enrolled in the current study compared to 5/462 (1.1%) in the Canadian point prevalence study.[12] This higher prevalence may have been related to outbreaks occurring on various hospital wards during the study period and the fact that 23% of patients were transferred into the ICU from these areas (Table 1). Conclusion This study describes antimicrobial consumption solely in an ICU setting using the DOT/1000PD methodology, which to our knowledge has not been previously reported, and therefore provides reference information for other centres interested in using this measurement unit. In addition, the relative contribution of empirical, directed and prophylactic therapy to antimicrobial consumption is quantified. The importance of identifying individualized targets for antimicrobial stewardship initiatives is also illustrated. With respect to the study ICU, these include strategies that focus on empirical therapy, prolonged durations of empirical therapy particularly with carbapenems, extended durations of surgical prophylaxis, dose optimization of frequently used agents such as piperacillin/tazobactam and vancomycin and parenteral to enteral interchange. While the majority of these findings are consistent with focus areas identified by the IDSA recommendations on antimicrobial stewardship,[4] the important contribution of empirical therapy (versus directed and prophylaxis) to antimicrobial consumption is noteworthy. Ongoing measurement and reporting of antimicrobial consumption and microbiological resistance in the ICU setting will identify successes from stewardship initiatives as well as new opportunities for continual improvement. Declarations Conflict of interest The Author(s) declare(s) that they have no conflicts of interest to disclose. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Acknowledgements The authors express their gratitude for statistical support to Stacy A. Voils, Critical Care Clinical Pharmacy Specialist, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals. The results of this study were presented as a poster presentation at the Professional Practice Conference of the Canadian Society of Hospital Pharmacists in Toronto, ON, on 30 January 2011. References 1 Zhanel GG et al. Antimicrobial-resistant pathogens in intensive care units in Canada: results of the Canadian National Intensive Care Unit (CAN-ICU) study, 2005–2006 . Antimicrob Agents Chemother 2008 ; 52 : 1430 – 1437 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Hanberger H et al. Surveillance of microbial resistance in European intensive care units: a first report from the Care-ICU programme for improved infection control . Intensive Care Med 2009 ; 35 : 91 – 100 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Singh N , Yu VL. Rational empiric antibiotic prescription in the ICU . Chest 2000 ; 117 : 1496 – 1499 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Dellit TH et al. 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Google Scholar Crossref Search ADS PubMed WorldCat © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society
TI - Antimicrobial use in a critical care unit: a prospective observational study
JF - International Journal of Pharmacy Practice
DO - 10.1111/j.2042-7174.2011.00176.x
DA - 2018-06-01
UR - https://www.deepdyve.com/lp/oxford-university-press/antimicrobial-use-in-a-critical-care-unit-a-prospective-observational-SlDTI7IVb8
SP - 164
EP - 171
VL - 20
IS - 3
DP - DeepDyve
ER -