Antimicrobial drug use in three Canadian general hospitals THOMAS L. PERRY, MD; GORDON H. GUYATT*
Total amounts of antimicrobial drugs used to treat inpatients during 1975 were calculated for three Canadian general hospitals, one of them the principal teaching hospital of a medical school. Use of drugs was compared with that reported for Boston City Hospital during periods when antimicrobial therapy was and was not supervised by infectious disease consultants. Ampicillin, tetracyclines, cephalosporins, erythromycin and aminoglycosides for prophylactic oral administration were used excessively in the three hospitals. The degree of overuse was comparable to that at Boston City Hospital during years when drug use was uncontrolled. Overuse or improper choice of antimicrobial drugs decreases the quality of patient care and increases its cost. More rigorous education is needed for both medical students and practising physicians in the rational use of antimicrobial drugs. Informal consultation with an infectious disease unit should be required before certain overly popular or toxic antibiotics are administered to hospitalized patients.
qu'on a signale pour le Boston City Hospital durant les periodes respectives ou l'antibiotherapie etait ou n'etait pas sous Ia surveillance de consultants en maladies infectieuses. L'ampicilline, les tetracyclines, les cephalosporines, l6rythromycine et les aminoglycosides administr6s oralement pour fin prophylactique ont 6te utilises excessivement dans les trois h8pitaux. Lexageration dans lemplol a ete comparable a celle du Boston City Hospital pour les annees ou lutilisation des medicaments ne faisait l.objet d'aucun contr8le. L.emploi excessif ou le choix non judicieux des m6dicaments antimicrobiens diminuent Ia qualit6 des soins aux patients et en augmentent le coOt. Pour les etudiants en medecine aussi bien que pour les medecins en pratique une education plus rigoureuse dans lutilisation rationelle des antimicrobiens simpose. On devrait exiger qu'une consultation non officielle soit prise aupres d.une unit6 de maladies infectieuses avant que certains antibiotiques trop populaires ou trop toxiques ne solent administr6s a des patients hospitalises.
On a calcul6 Ia somme totale des m6dlcaments antimicrobiens utilises au cours de 1975 pour traiter des patients hospitalis6s dans trois h6pitaux g6n6raux canadiens, dont l'un est le principal h6pital universitaire aff1116 & une 6cole de m6decine. L'emploi de ces medicaments a 6t6 compar6 & celul
Careful studies have documented the widespread overuse of antimicrobial drugs prevalent both in the community and in hospitals.1'2 Unnecessary use of antimicrobial drugs within hospitals is harmful for several reasons. The emergence of resistant pathogens in patients and in the hospital environment is encouraged.3'4 Life-endangering superinfections may occur in some patients, especially Staphylococcus aureus enteritis and systemic infections by Candida albicans.5 Approximately 5% of hospitalized patients given an antibiotic have some adverse reaction to the drug,2 and about half of these reactions
From the department of pharmacology, University of British Columbia 6Fourth.year medical student at McMaster University Reprint requests to: Dr. Thomas L. Perry, Department of pharmacology, University of British Columbia, Vancouver, BC V6T 1W5
result in a lengthening of the patient's stay in hospital. Overuse of antimicrobial drugs not only has a deleterious effect on patients in hospitals but also contributes to the rapidly escalating costs of health care, since these drugs may account for anywhere from 20 to 35% of hospital pharmacy expenses."6 Studies in several American hospitals have shown that the requirement of informal consultation with an infectious disease unit before antimicrobial drugs are prescribed for hospitalized patients can lead to substantial decreases in the use of some of these drugs."6 We have surveyed the use of antimicrobial drugs in three British Columbia general hospitals during 1975 and compared this use with that at Boston City Hospital during periods when antibiotic therapy was and was not supervised by infectious disease consultants.6 Methods Three general hospitals in the Vancouver area were studied. The Vancouver General Hospital (VGH) is a large city hospital that not only provides routine hospital care for residents of the city but also serves as the main centre for tertiary care of patients with serious or unusual illnesses referred from communities elsewhere in British Columbia. VGH is the chief institution in which University of British Columbia medical students receive their clinical training, about 25% of its beds being on teaching wards under university supervision. Admissions to VGH totalled 50 131 in 1975. That year Lions Gate Hospital (LGH) admitted 17 030 patients and Burnaby General Hospital (BGH) admitted 12629 patients. The two smaller general hospitals serve suburban areas of metropoli-
CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116 253
tan Vancouver; neither is associated with the university for teaching purposes. The total amounts of various antimicrobial drugs purchased by each hospital during 1975 were obtained from the pharmacy records. These figures closely approximate the actual amounts of drugs administered to hospital inpatients during the year. Drugs used for the treatment of tuberculosis, fungal infections and viral infections were not recorded. Figures on topical antibiotic use were available for only one hospital (BGH). Results
Antimicrobial drugs received by patients admitted to the three hospitals during 1975 are listed in Table I. Chemically or therapeutically related antimicrobials are grouped to simplify the table. These drugs accounted for 23 .65% of total drug purchases by the pharmacy at VGH. during 1975.
Use of four groups of antibiotics at VGH in 1975 and at Boston City Hospital during recent years is compared in Table II. (McGowan and Finland8 compared the use of selected antibiotics at Boston City Hospital during years when justification for choice of the antibiotic was required before it could be prescribed, and during years when antibiotic use was uncontrolled.) Discussion Use of most antimicrobial drugs was greater at VGH, a university-based hospital, than at the two nonteaching community hospitals. The greater use of the penicillinase-resistant penicillins and of the cephalosporins at VGH may have reflected a different patient population, a greater proportion of patients at that hospital having postoperative and other severe infections caused, respectively, by penicillinase-producing S. aureus and gram-negative organisms.
254 CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116
However, the use of aminoglycoside antibiotics (for parenteral administration), carbenicillin, polymyxin B and colistimethate, which are appropriate for severe gram-negative infections, was not substantially greater at VGH than at the two community general hospitals. Several antibiotics not noted for their efficacy in severe and unLisual infections (ampicillin, erythromycin and tetracyclines) were used more heavily at VGH than at one or both of the nonteaching community hospitals. All this suggests that input from a medical school may do little to prevent overuse of antimicrobial drugs in a large general hospital. The same conclusion can be drawn from experience at Boston City Hospital (a teaching base for three medical schools), where overuse of certain antibiotics was demonstrated clearly during periods when no scientific justification was required for their use.6 There are numerous examples in Table I of chemotherapeutic practices that are difficult to justify from present pharmacologic and bacteriologic concepts. Oral therapy with neomycin, kanamycin, succinylsulfathiazole and phthalylsulfathiazole appears to have been extensive at all three hospitals, especially VGH and BGH. These drugs are used prophylactically by some surgeons to "sterilize'. the large bowel prior to elective surgical procedures on the colon. Controlled studies, however, have repeatedly failed to demonstrate that this procedure reduces the incidence of postoperative infection or the mortality after operations on the large bowel, and it increases the danger of serious superinfections.7 Oral therapy with antibiotics is justifiable for decreasing the bacterial flora of the gut in patients with hepatic encephalopathy, but the amounts of these drugs used at VGH and BGH in 1975 far exceeded that required for this indication. An important hazard of prophylactic oral administration of aminoglycoside antibiotics before an operation is that gram-negative organisms in the lumen of the bowel may become resistant to one or more aminoglycosides, and this resistance may be passed to other species of gram-negative enteric pathogens by means of R factors.8-10 Oral administration of neomycin or kanamycin provides a strong selective pressure in favour of resistant bacteria by preventing the growth of all sensitive cells. As the normal nonpathogenic flora of the gut is decreased, massive overgrowth of drug-resistant pathogenic organisms can occur, and this may lead to tissue invasion by enteric pathogens. Gram-negative bacteremia, which was uncommon prior to the antibiotic era, is estimated to occur now in up to 1% of all hospitalized patients in North
America and the mortality is 30 to 50% . Unnecessarily toxic antimicrobial agents were used in the three general hospitals during 1975. Of the cephalosporin antibiotics cephaloridine accounted for 15% of the total use at LGH and 23% at BGH. Cephaloridine is no more effective therapeutically than are cephalothin and cephazolin administered parenterally, but it has much greater renal toxicity than any other cephalosporin." A substantial amount of sulfadimethoxine was given to patients at VGH. This sulfonamide is excreted relatively slowly by the kidneys. Therefore, it might be expected to be somewhat less useful than sulfisoxazole or trisulfapyrimidines in the treatment of most urinary tract infections, where high urinary concentrations of sulfonamide are desired. Its slow excretion from the body, however, prolongs toxic reactions to sulfonamide when these occur. In the United States sulfadimethoxine has been withdrawn from the market because of the high incidence of severe exudative erythema multiforme (Stevens-Johnson syndrome) resulting from its use.13 Neomycin used topically on the skin or mucous membranes sometimes induces hypersensitivity not only to itself but also to more therapeutically important aminoglycosides (kanamycin, gentamicm and tobramycin).'4"' Patients thus rendered hypersensitive may be unable to tolerate parenteral administration of aminoglycosides during later illnesses when such therapy might prove lifesaving. The heavy use of neomycin ointment at BGH was clearly unwise. The use of four antimicrobial agents - ampicillin, tetracyclines, cephalosporins and erythromycin - was strikingly high during 1975, especially at VGH. If one assumes that an average therapeutic course of ampicillin or amoxicillin for an adult patient consists of 28 g (2 g/d for 14 days), more than 7% of all patients admitted to VGH received full ampicillin treatment. Therapy with ampicillin is more frequently complicated by drug rashes than therapy with any other form of penicillin. More important, its overuse can lead to the emergence of ampicillin-resistant strains of previously sensitive pathogens, as demonstrated by the widespread appearance of ampicillin resistance in Hemophilus influenzae starting in 1974.16 Similar calculations indicate that over 4% of patients admitted to VGH received a full course of a tetracycline (assuming an average regimen of 1 g/d for 10 days) and that 3% of patients admitted to VGH received a full course of a cephalosporin (assuming 3 g/d for 10 days). A tetracycline is rarely the antimicrobial drug of first or second choice for
infections encountered in Canadian reveal similar conditions in general hoshospitals.17"8 It seems likely that the pitals elsewhere in Canada. Medical overuse of tetracychnes in hospitalized school affiliation does not necessarily patients is comparable to that docu- correct such overuse of drugs. If we mented2 for ambulatory patients in the are to avoid such future tragedies as community. patients who have infections that no Although erythromycin is a rather longer respond to the antimicrobial nontoxic drug, it is a first-choice anti- drugs at hand, and if we are to halt biotic only for the treatment of Myco- the rapid increase in the costs of hosplasma infections and as an alternative pital care, corrective steps must be to penicillin G or V for the treatment taken. of infections caused by Streptococcus In the United States the National pyogenes or Diplococcus pneumoniae Antibiotic Therapy Test recently taken when these develop in patients known by more than 4500 physicians demto be allergic to penicillin.'7"6 The pro- onstrated widespread deficiencies of portion of patients allergic to penicillin knowledge in the use of antimicrobial has been reported to vary between 0.7 drugs.'0 Resident physicians and doctors and 10% . Thus the ratio of use of in practice for 5 years or less scored penicillin G and V to that of erythro- better than did physicians in practice mycin in a hospital might reasonably for 15 years or more. Internists and be expected to vary between 100 and physicians specializing in infectious dis10. Calculations for VGH indicate that ease obtained better scores than did use of these penicillins was only four surgeons or family doctors. We suggest times as great as that of erythromycin. that more attention be paid to rigorous This anomaly is partly explained by and persistent education of medical the unorthodox use at VGH of erythro- students and practising physicians in mycin, in addition to neomycin and the rational choice of antimicrobial kanamycin, for "sterilization" of the drugs. More emphasis should be placed bowel prior to surgical procedures. on the scientific basis for the ecologic McGowan and Finland6 have re- havoc that can be caused by abuse of ported the substantial reduction in anti- these agents. Effective means must be biotic use that can occur in a general found for extending such education to hospital when choice of antibiotic must physicians who have been in practice first be justified by verbal consultation for some years. Regular reading of with an expert in infectious disease. publications like The Medical Letter, Unfortunately, this effect is reversible, which continually updates information as demonstrated by the striking in- on the clinical use of drugs, should be crease in use of ampicillin and penicil- encouraged. linase-resistant penicillins at Boston However, better education alone may City Hospital when justification for not be enough. Although residents pertheir rational use was no longer re- formed better than did physicians of quired. The use of ampicillin at VGH any other age group on the National in 1975 was similar to that at Boston Antibiotic Therapy Test,'0 data from City Hospital during years in which Boston City Hospital6 and from Vanno controls were exerted to prevent its couver General Hospital do not indioveruse. Cephalosporins were used cate that this superior knowledge is twice as heavily at VGH as at Boston directly translated into superior medical City Hospital during a recent period of practice. Apparently, even with the best controlled use. On the other hand, of teaching, some physicians tend to penicillinase-resistant penicillins were become careless, unthinking or frightused less extensively at VGH than at ened. and can misuse drugs. Many Boston City Hospital when use was tin- medical students have had experiences controlled in 1972. Chloramphenicol, like that of a young woman who rean antibiotic with severe potential toxi- cently protested when her family doccity, appears to have been used far tor gave her tetracycline for what more cautiously at VGH than at Bos- seemed obviously a viral respiratory ton City Hospital. tract infection. His answer was: "I The sort of comparisons we have don't care what the studies say. I know made might be criticized on the tetracycline works against viruses." grounds that patient populations in gen- Some form of effective peer pressure eral hospitals in Vancouver and Boston may be needed to combat such unmay differ, and that the patterns of scientific attitudes. We believe that esbacterial drug resistance as well as the tablishment of infectious disease units range of antimicrobial drugs available in larger hospitals and the requirement to physicians have changed over the of informal consultation before certain last 9 years. Nevertheless, we believe overly popular, toxic or expensive antithat sober appraisal of the data pre- microbials are used might prove as sented suggests that antimicrobial drugs valuable in Canadian hospitals as it did are used excessively and sometimes un- in Boston.6 This need not infringe on wisely within general hospitals in Van- the individual physician's right to make couver. It is likely that surveys would the final decision as to what drug, if CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116 255
any, his patient is given. But he should make this decision having had the benefit of the best available up-tc-date information. We thank Harry Smythe, Jack Dancey and Don Clark, the pharmacists of the three hospitals studied, for their friendly cooperation. We also thank Drs. James G Foulks, Frederick J. Roberts and Harvey D. Sanders for helpful discussions. References I. KUNIN CM, TUPAsI T, CRAIG WA: Use of antibiotics. A brief exposition of the problem and some tentative solutions. Anh Intern Med 79: 555, 1973 2. SIMMONs HE, STOLLEY PD: This is medical progress? Trends and consequences of anti-
biotic use in the United States. JAMA 227: 1023, 1974 3. FINLAND M: Changing ecology of bacterial infections as related to antibacterial therapy. J Infect Dis 122: 419, 1970 4. McCAsE WR, KREGER BE, iOHN5 M: Typespecific and cross-reactive antibodies in gramnegative bacteremia. N Engi J Med 287: 261, 1972 5. WEiNsrEi.i L, MUSHER DM: Antibiotic induced superinfection. J Infect Dis 119: 662, 1969 6. MCGOWAN
7. 8. 9. 10.
JE JR,
FINLAND M:
Usage
of
antibiotics in a general hospital: effect of requiring justification. .! infect Dis 130: 165, 1974 WEiNsTEiN L: Antimicrobial agents, in The Pharmacological Basis of Therapeutics, 5th ed, GOODMAN LS, GILMAN A (eds), New York, Macmillan, 1975, pp 1105-19 WATANABE T: Infectious drug resistance in bacteria. N Engl I Med 275: 888, 1966 Mrrsui.siu 5: The R factors. I Infect Dis 119: 89, 1969 GOLDSTEIN A, ARONOW L, KALMAN SM: Principles of Drug Action: The Basis of Pharmacology, 2nd ed, New York, Wiley, 1974, pp 517-25
Ii. WOLFF SM, BENNETT JV: Gram-negative-rod bacteremia. N Engi J Med 291: 733, 1974 12. WEINSTEIN L: Antimicrobial agents, in The Pharmacological Basis of Therapeutics, op cit, pp 1163-4 13. Idem: in The Pharmacological Basis of Therapeutics, op cit, p 1119 14. Hypersensitivity skin reactions due to neomycin. Med Lea Drugs Ther 9: 71, 1967 15. Topical neomycin. Med Lea Drugs Ther 15: 101, 1973 16. THOMAS WJ, MCREYNOLD5 JW, MOCK CR, et al: Ampicillin-resistant Haemophilus influenzae meningitis. Lancet 1: 313, 1974 17. WEINSTEIN L: Antimicrobial agents, In The Pharmacological Basis of Therapeutics, op cit, pp 1096-1103 18. Handbook of Antimicrobial Therapy, rev ed, New Rochelle, NY, The Medical Letter, 1976 19. IDSOE 0, GUTHE T, WILLcox RR, et al: Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull WHO 38: 159, 1968 20. NEU HC, HOWREY SP: Testing the physician s knowledge of antibiotic use: self-assessment and learning via videotape. N Engl I Med 293: 1291. 1975
Rational and irrational use of antibiotics in a Canadian teaching hospital MICHAEL R. ACHONG,* B SC, MB, FRCP[C]; BONNIE A. HAUSER,t B SC PHM; JUDY L. KRUSKY,t B SC PHM
Parenteral therapy with gentamicin, cloxacillin, ampicillin and cephalothin was surveyed on a surgical, a gynecologic and a medical ward of a teaching hospital. During a 3-month period 219 patients (12.90/o of the total number admitted to the three wards) received at least one of the four antibiotics parenterally. Ampicillin and gentamicin were used most frequently on the three wards when the indication for therapy was either infection or empirical use. Cephalothin was used most frequently for prophylaxis in the gynecologic and surgical patients; no medical patient received this drug. Overall, therapy was assessed to be irrational in 42.0, 50.0 and 12.00/o of the surgical, gynecologic and medical patients, respectively. Prophylaxis was the indication for therapy in 76.9 and 86.80/0 of the surgical and gynecologic patients, respectively, for whom the therapy was assessed to be irrational. On a etudie l'utilisation de Ia gentamicine, de Ia cloxacilline, de l'ampicilline et de Ia c6phalothine administr6es par vole parent6rale dans les services de soins chirurgicaux, gynecologiques et m6dicaux d'un h8pital universitaire. Au cours d'une p.riode de 3 mois 219 patients (12.90/o du From St. Joseph's Hospital, Hamilton 5Lecturer, department of medicine, McMaster University, Hamilton tClinical pharmacy resident, St. Joseph's Hospital Reprint requests to: Dr. MR. Achong, Department of medicine, St. Joseph's Hospital, Hamilton, Ont. L8N 1Y4
nombre total de sujets accuelilis dans les trois services) ont re.u au moms un des quatre antibiotiques par vole parenterale. L'ampicilline et Ia gentamicine ont ete utilisees le plus frequemment dans les trois services, soit pour le traitement d'une infection ou pour usage empirique. La cephalothine a et6 employee le plus souvent a des fins prophylactiques chez les patients de gynecologie et de chirurgie; aucun patient du service de soins m6dicaux n'a requ ce medicament. Au total, on a juge que le traitement avait et6 irrationnel dans 42.0, 50.0 et 12.00/0, respectivement, des cas de chirurgie, de gyn6cologie et de medecine generale. La prophylaxie a et6 l'indicatlon de traitement dans 76.9 et 86.80/0, respectivement, des cas de chirurgie et de gynecologie ou on a juge que le traitement etait irrationnel.
Concern has been expressed in recent years that the rapid increase in antibiotic use in hospital and community practice may be doing more harm than good."2 Surveys have shown that about one third of hospital patients receive systemic antibiotic therapy and that such therapy is often irrational."38 In community hospitals Scheckler and Bennett4 found that 62% of patients who received antibiotics showed no evidence of infection, and Roberts and Visconti6 assessed 65.6% of all antibiotic therapy as irrational and another 21.5% as questionable. The record is apparently no better in teaching hospitals, where prescribing practices might be expected to be exemplary. Thus,
256 CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116
Kunin, Tupasi and Craig1 found that in 51.5% of patients in a University of Virginia hospital either the antibiotic therapy was not indicated or the choice of drug or dosage was inappropriate. Because patterns of antibiotic use vary from hospital to hospital and, indeed, from time to time in the same hospital, Aagaard7 suggested that hospitals should identify their own prescribing patterns and problems in antibiotic therapy. This is the logical first step in any program aimed at making antibiotic therapy more rational. We report the results of a survey of antibiotic therapy on a surgical, a gynecologic and a medical ward of St. Joseph's Hospital, Hamilton, a teaching hospital affiliated with McMaster University. In 1975 $134200 - 24.9% of this hospital's drug budget - was spent on parenteral antibiotic therapy. Gentamicin, cloxacillin, ampicillin and cephalothin accounted for 34.4, 32.1, 10.5 and 9.9%, respectively, of this sum. We therefore chose to survey the parenteral use of these four antibiotics. Our aims were as follows: 1. To document the indications for parenteral antibiotic therapy on a surgical, a gynecologic and a medical ward of the hospital. 2. To describe the prescribing patterns of antibiotics administered parenterally. 3. To assess the extent to which parenteral antibiotic therapy was rational. Methods The survey was conducted over a 3-month period (Jan. 1, 1976 to Mar.
Total amounts of antimicrobial drugs used to treat inpatients during 1975 were calculated for three Canadian general hospitals, one of them the principal teaching hospital of a medical school. Use of drugs was compared with that reported for Boston City Hospital during periods when antimicrobial therapy was and was not supervised by infectious disease consultants. Ampicillin, tetracyclines, cephalosporins, erythromycin and aminoglycosides for prophylactic oral administration were used excessively in the three hospitals. The degree of overuse was comparable to that at Boston City Hospital during years when drug use was uncontrolled. Overuse or improper choice of antimicrobial drugs decreases the quality of patient care and increases its cost. More rigorous education is needed for both medical students and practising physicians in the rational use of antimicrobial drugs. Informal consultation with an infectious disease unit should be required before certain overly popular or toxic antibiotics are administered to hospitalized patients.
qu'on a signale pour le Boston City Hospital durant les periodes respectives ou l'antibiotherapie etait ou n'etait pas sous Ia surveillance de consultants en maladies infectieuses. L'ampicilline, les tetracyclines, les cephalosporines, l6rythromycine et les aminoglycosides administr6s oralement pour fin prophylactique ont 6te utilises excessivement dans les trois h8pitaux. Lexageration dans lemplol a ete comparable a celle du Boston City Hospital pour les annees ou lutilisation des medicaments ne faisait l.objet d'aucun contr8le. L.emploi excessif ou le choix non judicieux des m6dicaments antimicrobiens diminuent Ia qualit6 des soins aux patients et en augmentent le coOt. Pour les etudiants en medecine aussi bien que pour les medecins en pratique une education plus rigoureuse dans lutilisation rationelle des antimicrobiens simpose. On devrait exiger qu'une consultation non officielle soit prise aupres d.une unit6 de maladies infectieuses avant que certains antibiotiques trop populaires ou trop toxiques ne solent administr6s a des patients hospitalises.
On a calcul6 Ia somme totale des m6dlcaments antimicrobiens utilises au cours de 1975 pour traiter des patients hospitalis6s dans trois h6pitaux g6n6raux canadiens, dont l'un est le principal h6pital universitaire aff1116 & une 6cole de m6decine. L'emploi de ces medicaments a 6t6 compar6 & celul
Careful studies have documented the widespread overuse of antimicrobial drugs prevalent both in the community and in hospitals.1'2 Unnecessary use of antimicrobial drugs within hospitals is harmful for several reasons. The emergence of resistant pathogens in patients and in the hospital environment is encouraged.3'4 Life-endangering superinfections may occur in some patients, especially Staphylococcus aureus enteritis and systemic infections by Candida albicans.5 Approximately 5% of hospitalized patients given an antibiotic have some adverse reaction to the drug,2 and about half of these reactions
From the department of pharmacology, University of British Columbia 6Fourth.year medical student at McMaster University Reprint requests to: Dr. Thomas L. Perry, Department of pharmacology, University of British Columbia, Vancouver, BC V6T 1W5
result in a lengthening of the patient's stay in hospital. Overuse of antimicrobial drugs not only has a deleterious effect on patients in hospitals but also contributes to the rapidly escalating costs of health care, since these drugs may account for anywhere from 20 to 35% of hospital pharmacy expenses."6 Studies in several American hospitals have shown that the requirement of informal consultation with an infectious disease unit before antimicrobial drugs are prescribed for hospitalized patients can lead to substantial decreases in the use of some of these drugs."6 We have surveyed the use of antimicrobial drugs in three British Columbia general hospitals during 1975 and compared this use with that at Boston City Hospital during periods when antibiotic therapy was and was not supervised by infectious disease consultants.6 Methods Three general hospitals in the Vancouver area were studied. The Vancouver General Hospital (VGH) is a large city hospital that not only provides routine hospital care for residents of the city but also serves as the main centre for tertiary care of patients with serious or unusual illnesses referred from communities elsewhere in British Columbia. VGH is the chief institution in which University of British Columbia medical students receive their clinical training, about 25% of its beds being on teaching wards under university supervision. Admissions to VGH totalled 50 131 in 1975. That year Lions Gate Hospital (LGH) admitted 17 030 patients and Burnaby General Hospital (BGH) admitted 12629 patients. The two smaller general hospitals serve suburban areas of metropoli-
CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116 253
tan Vancouver; neither is associated with the university for teaching purposes. The total amounts of various antimicrobial drugs purchased by each hospital during 1975 were obtained from the pharmacy records. These figures closely approximate the actual amounts of drugs administered to hospital inpatients during the year. Drugs used for the treatment of tuberculosis, fungal infections and viral infections were not recorded. Figures on topical antibiotic use were available for only one hospital (BGH). Results
Antimicrobial drugs received by patients admitted to the three hospitals during 1975 are listed in Table I. Chemically or therapeutically related antimicrobials are grouped to simplify the table. These drugs accounted for 23 .65% of total drug purchases by the pharmacy at VGH. during 1975.
Use of four groups of antibiotics at VGH in 1975 and at Boston City Hospital during recent years is compared in Table II. (McGowan and Finland8 compared the use of selected antibiotics at Boston City Hospital during years when justification for choice of the antibiotic was required before it could be prescribed, and during years when antibiotic use was uncontrolled.) Discussion Use of most antimicrobial drugs was greater at VGH, a university-based hospital, than at the two nonteaching community hospitals. The greater use of the penicillinase-resistant penicillins and of the cephalosporins at VGH may have reflected a different patient population, a greater proportion of patients at that hospital having postoperative and other severe infections caused, respectively, by penicillinase-producing S. aureus and gram-negative organisms.
254 CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116
However, the use of aminoglycoside antibiotics (for parenteral administration), carbenicillin, polymyxin B and colistimethate, which are appropriate for severe gram-negative infections, was not substantially greater at VGH than at the two community general hospitals. Several antibiotics not noted for their efficacy in severe and unLisual infections (ampicillin, erythromycin and tetracyclines) were used more heavily at VGH than at one or both of the nonteaching community hospitals. All this suggests that input from a medical school may do little to prevent overuse of antimicrobial drugs in a large general hospital. The same conclusion can be drawn from experience at Boston City Hospital (a teaching base for three medical schools), where overuse of certain antibiotics was demonstrated clearly during periods when no scientific justification was required for their use.6 There are numerous examples in Table I of chemotherapeutic practices that are difficult to justify from present pharmacologic and bacteriologic concepts. Oral therapy with neomycin, kanamycin, succinylsulfathiazole and phthalylsulfathiazole appears to have been extensive at all three hospitals, especially VGH and BGH. These drugs are used prophylactically by some surgeons to "sterilize'. the large bowel prior to elective surgical procedures on the colon. Controlled studies, however, have repeatedly failed to demonstrate that this procedure reduces the incidence of postoperative infection or the mortality after operations on the large bowel, and it increases the danger of serious superinfections.7 Oral therapy with antibiotics is justifiable for decreasing the bacterial flora of the gut in patients with hepatic encephalopathy, but the amounts of these drugs used at VGH and BGH in 1975 far exceeded that required for this indication. An important hazard of prophylactic oral administration of aminoglycoside antibiotics before an operation is that gram-negative organisms in the lumen of the bowel may become resistant to one or more aminoglycosides, and this resistance may be passed to other species of gram-negative enteric pathogens by means of R factors.8-10 Oral administration of neomycin or kanamycin provides a strong selective pressure in favour of resistant bacteria by preventing the growth of all sensitive cells. As the normal nonpathogenic flora of the gut is decreased, massive overgrowth of drug-resistant pathogenic organisms can occur, and this may lead to tissue invasion by enteric pathogens. Gram-negative bacteremia, which was uncommon prior to the antibiotic era, is estimated to occur now in up to 1% of all hospitalized patients in North
America and the mortality is 30 to 50% . Unnecessarily toxic antimicrobial agents were used in the three general hospitals during 1975. Of the cephalosporin antibiotics cephaloridine accounted for 15% of the total use at LGH and 23% at BGH. Cephaloridine is no more effective therapeutically than are cephalothin and cephazolin administered parenterally, but it has much greater renal toxicity than any other cephalosporin." A substantial amount of sulfadimethoxine was given to patients at VGH. This sulfonamide is excreted relatively slowly by the kidneys. Therefore, it might be expected to be somewhat less useful than sulfisoxazole or trisulfapyrimidines in the treatment of most urinary tract infections, where high urinary concentrations of sulfonamide are desired. Its slow excretion from the body, however, prolongs toxic reactions to sulfonamide when these occur. In the United States sulfadimethoxine has been withdrawn from the market because of the high incidence of severe exudative erythema multiforme (Stevens-Johnson syndrome) resulting from its use.13 Neomycin used topically on the skin or mucous membranes sometimes induces hypersensitivity not only to itself but also to more therapeutically important aminoglycosides (kanamycin, gentamicm and tobramycin).'4"' Patients thus rendered hypersensitive may be unable to tolerate parenteral administration of aminoglycosides during later illnesses when such therapy might prove lifesaving. The heavy use of neomycin ointment at BGH was clearly unwise. The use of four antimicrobial agents - ampicillin, tetracyclines, cephalosporins and erythromycin - was strikingly high during 1975, especially at VGH. If one assumes that an average therapeutic course of ampicillin or amoxicillin for an adult patient consists of 28 g (2 g/d for 14 days), more than 7% of all patients admitted to VGH received full ampicillin treatment. Therapy with ampicillin is more frequently complicated by drug rashes than therapy with any other form of penicillin. More important, its overuse can lead to the emergence of ampicillin-resistant strains of previously sensitive pathogens, as demonstrated by the widespread appearance of ampicillin resistance in Hemophilus influenzae starting in 1974.16 Similar calculations indicate that over 4% of patients admitted to VGH received a full course of a tetracycline (assuming an average regimen of 1 g/d for 10 days) and that 3% of patients admitted to VGH received a full course of a cephalosporin (assuming 3 g/d for 10 days). A tetracycline is rarely the antimicrobial drug of first or second choice for
infections encountered in Canadian reveal similar conditions in general hoshospitals.17"8 It seems likely that the pitals elsewhere in Canada. Medical overuse of tetracychnes in hospitalized school affiliation does not necessarily patients is comparable to that docu- correct such overuse of drugs. If we mented2 for ambulatory patients in the are to avoid such future tragedies as community. patients who have infections that no Although erythromycin is a rather longer respond to the antimicrobial nontoxic drug, it is a first-choice anti- drugs at hand, and if we are to halt biotic only for the treatment of Myco- the rapid increase in the costs of hosplasma infections and as an alternative pital care, corrective steps must be to penicillin G or V for the treatment taken. of infections caused by Streptococcus In the United States the National pyogenes or Diplococcus pneumoniae Antibiotic Therapy Test recently taken when these develop in patients known by more than 4500 physicians demto be allergic to penicillin.'7"6 The pro- onstrated widespread deficiencies of portion of patients allergic to penicillin knowledge in the use of antimicrobial has been reported to vary between 0.7 drugs.'0 Resident physicians and doctors and 10% . Thus the ratio of use of in practice for 5 years or less scored penicillin G and V to that of erythro- better than did physicians in practice mycin in a hospital might reasonably for 15 years or more. Internists and be expected to vary between 100 and physicians specializing in infectious dis10. Calculations for VGH indicate that ease obtained better scores than did use of these penicillins was only four surgeons or family doctors. We suggest times as great as that of erythromycin. that more attention be paid to rigorous This anomaly is partly explained by and persistent education of medical the unorthodox use at VGH of erythro- students and practising physicians in mycin, in addition to neomycin and the rational choice of antimicrobial kanamycin, for "sterilization" of the drugs. More emphasis should be placed bowel prior to surgical procedures. on the scientific basis for the ecologic McGowan and Finland6 have re- havoc that can be caused by abuse of ported the substantial reduction in anti- these agents. Effective means must be biotic use that can occur in a general found for extending such education to hospital when choice of antibiotic must physicians who have been in practice first be justified by verbal consultation for some years. Regular reading of with an expert in infectious disease. publications like The Medical Letter, Unfortunately, this effect is reversible, which continually updates information as demonstrated by the striking in- on the clinical use of drugs, should be crease in use of ampicillin and penicil- encouraged. linase-resistant penicillins at Boston However, better education alone may City Hospital when justification for not be enough. Although residents pertheir rational use was no longer re- formed better than did physicians of quired. The use of ampicillin at VGH any other age group on the National in 1975 was similar to that at Boston Antibiotic Therapy Test,'0 data from City Hospital during years in which Boston City Hospital6 and from Vanno controls were exerted to prevent its couver General Hospital do not indioveruse. Cephalosporins were used cate that this superior knowledge is twice as heavily at VGH as at Boston directly translated into superior medical City Hospital during a recent period of practice. Apparently, even with the best controlled use. On the other hand, of teaching, some physicians tend to penicillinase-resistant penicillins were become careless, unthinking or frightused less extensively at VGH than at ened. and can misuse drugs. Many Boston City Hospital when use was tin- medical students have had experiences controlled in 1972. Chloramphenicol, like that of a young woman who rean antibiotic with severe potential toxi- cently protested when her family doccity, appears to have been used far tor gave her tetracycline for what more cautiously at VGH than at Bos- seemed obviously a viral respiratory ton City Hospital. tract infection. His answer was: "I The sort of comparisons we have don't care what the studies say. I know made might be criticized on the tetracycline works against viruses." grounds that patient populations in gen- Some form of effective peer pressure eral hospitals in Vancouver and Boston may be needed to combat such unmay differ, and that the patterns of scientific attitudes. We believe that esbacterial drug resistance as well as the tablishment of infectious disease units range of antimicrobial drugs available in larger hospitals and the requirement to physicians have changed over the of informal consultation before certain last 9 years. Nevertheless, we believe overly popular, toxic or expensive antithat sober appraisal of the data pre- microbials are used might prove as sented suggests that antimicrobial drugs valuable in Canadian hospitals as it did are used excessively and sometimes un- in Boston.6 This need not infringe on wisely within general hospitals in Van- the individual physician's right to make couver. It is likely that surveys would the final decision as to what drug, if CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116 255
any, his patient is given. But he should make this decision having had the benefit of the best available up-tc-date information. We thank Harry Smythe, Jack Dancey and Don Clark, the pharmacists of the three hospitals studied, for their friendly cooperation. We also thank Drs. James G Foulks, Frederick J. Roberts and Harvey D. Sanders for helpful discussions. References I. KUNIN CM, TUPAsI T, CRAIG WA: Use of antibiotics. A brief exposition of the problem and some tentative solutions. Anh Intern Med 79: 555, 1973 2. SIMMONs HE, STOLLEY PD: This is medical progress? Trends and consequences of anti-
biotic use in the United States. JAMA 227: 1023, 1974 3. FINLAND M: Changing ecology of bacterial infections as related to antibacterial therapy. J Infect Dis 122: 419, 1970 4. McCAsE WR, KREGER BE, iOHN5 M: Typespecific and cross-reactive antibodies in gramnegative bacteremia. N Engi J Med 287: 261, 1972 5. WEiNsrEi.i L, MUSHER DM: Antibiotic induced superinfection. J Infect Dis 119: 662, 1969 6. MCGOWAN
7. 8. 9. 10.
JE JR,
FINLAND M:
Usage
of
antibiotics in a general hospital: effect of requiring justification. .! infect Dis 130: 165, 1974 WEiNsTEiN L: Antimicrobial agents, in The Pharmacological Basis of Therapeutics, 5th ed, GOODMAN LS, GILMAN A (eds), New York, Macmillan, 1975, pp 1105-19 WATANABE T: Infectious drug resistance in bacteria. N Engl I Med 275: 888, 1966 Mrrsui.siu 5: The R factors. I Infect Dis 119: 89, 1969 GOLDSTEIN A, ARONOW L, KALMAN SM: Principles of Drug Action: The Basis of Pharmacology, 2nd ed, New York, Wiley, 1974, pp 517-25
Ii. WOLFF SM, BENNETT JV: Gram-negative-rod bacteremia. N Engi J Med 291: 733, 1974 12. WEINSTEIN L: Antimicrobial agents, in The Pharmacological Basis of Therapeutics, op cit, pp 1163-4 13. Idem: in The Pharmacological Basis of Therapeutics, op cit, p 1119 14. Hypersensitivity skin reactions due to neomycin. Med Lea Drugs Ther 9: 71, 1967 15. Topical neomycin. Med Lea Drugs Ther 15: 101, 1973 16. THOMAS WJ, MCREYNOLD5 JW, MOCK CR, et al: Ampicillin-resistant Haemophilus influenzae meningitis. Lancet 1: 313, 1974 17. WEINSTEIN L: Antimicrobial agents, In The Pharmacological Basis of Therapeutics, op cit, pp 1096-1103 18. Handbook of Antimicrobial Therapy, rev ed, New Rochelle, NY, The Medical Letter, 1976 19. IDSOE 0, GUTHE T, WILLcox RR, et al: Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull WHO 38: 159, 1968 20. NEU HC, HOWREY SP: Testing the physician s knowledge of antibiotic use: self-assessment and learning via videotape. N Engl I Med 293: 1291. 1975
Rational and irrational use of antibiotics in a Canadian teaching hospital MICHAEL R. ACHONG,* B SC, MB, FRCP[C]; BONNIE A. HAUSER,t B SC PHM; JUDY L. KRUSKY,t B SC PHM
Parenteral therapy with gentamicin, cloxacillin, ampicillin and cephalothin was surveyed on a surgical, a gynecologic and a medical ward of a teaching hospital. During a 3-month period 219 patients (12.90/o of the total number admitted to the three wards) received at least one of the four antibiotics parenterally. Ampicillin and gentamicin were used most frequently on the three wards when the indication for therapy was either infection or empirical use. Cephalothin was used most frequently for prophylaxis in the gynecologic and surgical patients; no medical patient received this drug. Overall, therapy was assessed to be irrational in 42.0, 50.0 and 12.00/o of the surgical, gynecologic and medical patients, respectively. Prophylaxis was the indication for therapy in 76.9 and 86.80/0 of the surgical and gynecologic patients, respectively, for whom the therapy was assessed to be irrational. On a etudie l'utilisation de Ia gentamicine, de Ia cloxacilline, de l'ampicilline et de Ia c6phalothine administr6es par vole parent6rale dans les services de soins chirurgicaux, gynecologiques et m6dicaux d'un h8pital universitaire. Au cours d'une p.riode de 3 mois 219 patients (12.90/o du From St. Joseph's Hospital, Hamilton 5Lecturer, department of medicine, McMaster University, Hamilton tClinical pharmacy resident, St. Joseph's Hospital Reprint requests to: Dr. MR. Achong, Department of medicine, St. Joseph's Hospital, Hamilton, Ont. L8N 1Y4
nombre total de sujets accuelilis dans les trois services) ont re.u au moms un des quatre antibiotiques par vole parenterale. L'ampicilline et Ia gentamicine ont ete utilisees le plus frequemment dans les trois services, soit pour le traitement d'une infection ou pour usage empirique. La cephalothine a et6 employee le plus souvent a des fins prophylactiques chez les patients de gynecologie et de chirurgie; aucun patient du service de soins m6dicaux n'a requ ce medicament. Au total, on a juge que le traitement avait et6 irrationnel dans 42.0, 50.0 et 12.00/0, respectivement, des cas de chirurgie, de gyn6cologie et de medecine generale. La prophylaxie a et6 l'indicatlon de traitement dans 76.9 et 86.80/0, respectivement, des cas de chirurgie et de gynecologie ou on a juge que le traitement etait irrationnel.
Concern has been expressed in recent years that the rapid increase in antibiotic use in hospital and community practice may be doing more harm than good."2 Surveys have shown that about one third of hospital patients receive systemic antibiotic therapy and that such therapy is often irrational."38 In community hospitals Scheckler and Bennett4 found that 62% of patients who received antibiotics showed no evidence of infection, and Roberts and Visconti6 assessed 65.6% of all antibiotic therapy as irrational and another 21.5% as questionable. The record is apparently no better in teaching hospitals, where prescribing practices might be expected to be exemplary. Thus,
256 CMA JOURNAL/FEBRUARY 5, 1977/VOL. 116
Kunin, Tupasi and Craig1 found that in 51.5% of patients in a University of Virginia hospital either the antibiotic therapy was not indicated or the choice of drug or dosage was inappropriate. Because patterns of antibiotic use vary from hospital to hospital and, indeed, from time to time in the same hospital, Aagaard7 suggested that hospitals should identify their own prescribing patterns and problems in antibiotic therapy. This is the logical first step in any program aimed at making antibiotic therapy more rational. We report the results of a survey of antibiotic therapy on a surgical, a gynecologic and a medical ward of St. Joseph's Hospital, Hamilton, a teaching hospital affiliated with McMaster University. In 1975 $134200 - 24.9% of this hospital's drug budget - was spent on parenteral antibiotic therapy. Gentamicin, cloxacillin, ampicillin and cephalothin accounted for 34.4, 32.1, 10.5 and 9.9%, respectively, of this sum. We therefore chose to survey the parenteral use of these four antibiotics. Our aims were as follows: 1. To document the indications for parenteral antibiotic therapy on a surgical, a gynecologic and a medical ward of the hospital. 2. To describe the prescribing patterns of antibiotics administered parenterally. 3. To assess the extent to which parenteral antibiotic therapy was rational. Methods The survey was conducted over a 3-month period (Jan. 1, 1976 to Mar.
