While no attempt was made to assess formally the appropriateness of antibiotic prescribing patterns, antibiotic usage did appear to correspond to the clinical indications for which antimicrobial therapy was prescribed, as well as to the bacteria isolated from patients with infection. Active involvement of pharmacy, infectious disease and microbiology personnel may have also affected the appropriateness of antibiotic choice. Finally, the enforcement of strict infection control procedures in the CrCU may have influenced the low incidence of antibiotic resistance observed in the audit.
ICUs are often the target of surveillance programs and antimicrobial restrictions due to increased rates of bacterial resistance. Although it is difficult to make direct comparisons with other ICUs without detailed demographic information, the results of our study demonstrated a lower incidence of antimicrobial resistance among bacterial isolates of patients receiving parenteral antibiotics relative to reports from other American and Canadian sites. A similar study of resistance in Gram-negative bacilli in a 16-bed ICU in a Vancouver, British Columbia hospital demonstrated a much higher incidence of Gram-negative infections, 35% of which were associated with beta-lactamase-mediated resistance. This study, however, included burn patients, which may have accounted for these results. Another study of 1939 Gram- negative isolates from 20 Canadian ICUs also demonstrated a higher incidence of resistance, particularly to beta-lactam antibiotics and ciprofloxacin. Our CrCU appeared to have a fewer number of more difficult to treat organisms such as pseudomonal isolates (13.5%), compared with most ICUs where Pseudomonas species have been the primary pathogen, accounting for up to 28% of isolates. In addition, we also had a very low incidence of MRSA isolates compared with other sites. The findings in this study were reassuring in that the incidence of bacterial resistance among patients receiving antibiotics has remained low. Also, there were no outbreaks with multiply resistant organisms during the study, although the CrCU has experienced previous outbreaks, possibly due to the excessive use of broad-spectrum antibiotics.
The only study that has quantified microbial resistance rates relative to antibiotic use collected data on several antimicrobial-organism pairs from eight American hospitals (ICARE Project). Data from the ICUs studied demonstrated a strong correlation between the use of ceftazidime and both ceftazidime-resistant E cloacae and P aeruginosa. Surprisingly, there was no relationship between resistance in E cloacae and other third-generation cephalosporins. Furthermore, these relationships were not found in the non-ICU areas of the hospitals.
There were 759 admissions to the CrCU during the study. One-third of patients were admitted from the emergency department, 32% of patients came from the operating room and 35% were transferred to the CrCU from another ward or hospital. A total of 258 (32%) patients received parenteral antimicrobial therapy during their CrCU stay, including 75 medical, 105 surgical and 78 trauma patients. There were 340 courses of antibiotics administered; 226 were for treatment of infection and 114 were for surgical prophylaxis. The average duration of antimicrobial therapy for all patients included in the audit was 6.7 days (range one to 54 days). The most frequently prescribed antibiotic was cefazolin (47% of patients, 1098 g total use), followed by gentamicin (33%, 141 g), ceftriaxone (20%, 255 g), metronidazole (19%, 209 g), clindamycin (19%, 459 g) (Dalacin C, Pharmacia & Upjohn Inc, Mississauga, Ontario), cloxacillin (17%, 1913 g), cefuroxime (16%, 323 g) (Zinacef, Glaxo Canada Inc, Toronto, Ontario), vancomycin (15%, 256 g) (Vancocin, Eli Lilly Canada Inc, Scarborough, Ontario), ampicillin (14%, 1028 g) and tobramycin (12%, 81 g) (Table 1). The overall cost of all parenteral antibiotics during the audit was $57,854.35, which represented 18% of the total drug budget for the CrCU for that year.
The average length of stay for patients receiving antibiotics (10.7±14.7 days) was significantly higher than the length of stay of all patients admitted to the CrCU (4.7±8.0 days) during this period (P<0.01). There were 6.3 infections treated with antibiotics/100 patient days during the surveillance period. Of the patients who received antimicrobial therapy, 76% remained in the CrCU for more than 48 h.
At the time of the study, Sunnybrook Health Science Centre was a 982-bed (418 acute, 564 chronic), university-affiliated, adult tertiary care teaching hospital in Metropolitan Toronto. It is the largest level 1 trauma centre in Canada, with other major teaching programs that include aging, cardiovascular disease, oncology and trauma. At the time of the study, the CrCU was a 17-bed unit that admitted medical, surgical and trauma patients, the majority of whom required mechanical ventilation.
Data were prospectively collected over a one-year period, May 1, 1995 to April 30, 1996, from all patients admitted to the CrCU for more than one day and who received parenteral antimicrobial therapy. Information collected by daily chart review included site of infection, culture and antimicrobial susceptibility test results and length of stay. Duration of parenteral antibiotic usage, as well as total antibiotic acquisition costs, were also recorded.
The diagnosis of infection and choice of antimicrobial therapy were at the discretion of the medical staff in the CrCU. There was, however, significant input into antimicrobial prescribing by the Departments of Pharmacy, Microbiology and Infectious Diseases. This included daily attendance at patient rounds by a clinical pharmacist and weekly rounds with a mi- crobiologist. Table 1 includes all formulary antibiotics that were available for use in the CrCU. The medical staff in the CrCU was not aware that the audit was being performed.
Microbiological surveillance and parenteral antibiotic use in a critical care unit
The emergence of antimicrobial resistance over the past several decades has challenged the management of infections in hospitalized patients, and has led to increased morbidity, higher health care costs and prolonged hospitalizations. Hospitals are now frequently encountering outbreaks of resistant organisms such as vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Patients admitted to intensive care units, in particular, often become colonized with resistant organisms and may serve as the focus for hospital-wide bacterial resistance. The high prevalence of resistance in intensive care units (ICUs) has been attributed to the severity of illness of the patients, prolonged hospital stays, and the widespread use of invasive devices and broad spectrum antibiotics.
Fluconazole is one of the new imidazoles undergoing clinical trials for the treatment of fungal infections. We used fluconazole at a dose of 50 or 100 mg/day for the treatment of patients with persistent or disseminated coccidioidomycosis. Twelve of 14 patients had an initial favorable response, with definite improvement of clinical signs and symptoms of coccidioidal infection; however, five of 11 surviving patients suffered reactivation of their infections 9 days to 15 months after fluconazole was stopped.
Of the 12 who initially responded, only four remained free of coccidioidal disease. These patients have been followed for 10, 13, 15, and 18 months. One patient died of a myocardial infarction at the end of successful treatment of his fungal infection. Six of the 11 surviving responders had a relapse nine days to 15 months after treatment was stopped. Only one responder suffered a relapse while still receiving fluconazole. The clinical courses of the patients who had a relapse are summarized briefly.
Patient 3 had longstanding fibrocavitary disease. He previously had responded to amphotericin B, but suffered a relapse. A similar scenario followed treatment with ketoconazole. He then responded well to treatment with fluconazole (50 mg/day), with resolution of all pulmonary symptoms but minimal improvement in his roentgenogram. Eight months after fluconazole had been discontinued, the patient developed fever, weight loss, and a productive cough, and С immitis was again recovered from his sputum.