- Email: [email protected]
New strategies for the cost-effective use of antimicrobics
IIDNI Volume 5, Number 5, May 1986
Editor
Paul D. Hoeprich, MD Division of Infectious and Immunologic Diseases University of California, Davis Medical Center
Associate Editors
R u t h M. Lawrence, MD
Larry K. Picketing, MD
Charles W. Stratton, MD
Division of Infectious Diseases Texas Tech University Health Sciences Center
Program in Infectious Diseases and Clinical Microbiology The University of Texas Medical School at Houston
Department of Pathology Vanderbilt University Medical Center
New Strategies for the Cost-effective Use of Antimicrobics Charles W. Stratton, MD
()lllcll[!
New Strategies for the Cost-effective Use of Antimicrobics Charles W. Stratton CASE REPORT Sanford H. Robbins, Sally Calzada, and John Keiser
33
36
COMMENTS ON CURRENT PUBLICATIONS
Elsevier 0278-2316/86/$0.00 + 2.20
37
Vanderbilt University School of Medicine, Nashville, Tennessee
Medical practice in the 1980s is caught between advances in pharmaceutical agents and the demand for accountability. The introduction of new antimicrobics that are very costly, in comparison with older agents, has greatly complicated antimicrobial therapy. It is now possible to use antimicrobics correctly in a therapeutic sense, but to misuse them in an economic sense, by prescribing a more expensive agent when a less expensive agent would suffice. Nonetheless, recognition of new pathogens, increasing resistance of pathogens to older antimicrobics, and more complicated clinical problems have increased the need for the new agents. It is difficult for physicians not specializing in infectious diseases to keep abreast of changes in the triad of patients, pathogens, and antimicrobics. These changes, along with the recent emphasis on controlling
costs, argue for new strategies in the use of antimicrobics. Such strategies promise to be useful in controlling costs, when combined with an educational outreach program.
Familiarization Clinicians who prescribe antimicrobics need to invest time and energy beyond reading a package insert to gain familiarity with antimicrobial agents. For example, the dosing interval on the package insert may reflect the way the antimicrobic was studied, but does not necessarily represent the actual pharmacokinetics of the drug. Table 1 provides data regarding some commonly used antimicrobics that are often dosed more frequently than needed. The age of the patient may be important. The dosing of aminocyclitols was originally based on the pharmacokinetics of these drugs in young adults. However, when treat-
ISSN 0278-2316
IDINDN 5(5)33-40. 1986
34 Infectious Diseases Newsletter 5(5) May 1986 Table 1. Pharmacokinetics of Commonly Used Antimicrobics
Antimicrobic
Half-life in hours
Tetracycline Sulfamethoxazole Trimethoprim Vancomyein~ Metronidazole Amphotericin B"
6-12 8-10 10-12 ) 6- 9 6-10 24-48
Dosage interval in hours Conventional Pharmacologic 6
12
6 6 6 24
12 12 12 48
"Doses doubled when interval is doubled.
ing older patients who often have decreased renal function or diminished renal reserve, it may be safer to divide the total daily dose by two instead of three, giving a larger dose every 12 hours. This will result in higher peak levels (6-8 ~ g / m l for gentamicin and tobramycin) and lower trough levels. Lack of familiarity may mean that a newer agent with an advantage for a particular infection either is not used or is used incorrectly. The increased tissue penetration of the newer cephalosporins is a factor favoring their use in many kinds of bacterial meningitis and in pneumonias. Knowledge of the clinical results with the newer antipseudomonal fl-lactam agents leads to the conclusion that aminocyclitols must still be included in the treatment of serious pseudomonal infections. Glib labeling as to "generation" has in part contributed to inadequacy of understanding. The newer cephalosporins are quite diverse in spectrum, activity, and pharmacokinetic properties. The use of the terms "second-generation cephalosporin" or "third-generation cephalosporin" implies a similarity that simply does not exist. Antimicrobics must be thought of as drugs --individual agents that are chem-
ical entities--and not lumped as a "generation." To be familiar with an antimicrobic is to know its (1) spectrum of activity; (2) mechanism of action; (3) proven clinical efficacy; (4) pharmacokinetic properties; (5) side effects; and (6) cost. Assessment of Risk
There is need for improved assessment of risk in the use of antimicrobics for prophylaxis and treatment. Pneumonia in an adult cannot be treated without consideration of the patient's age. In the elderly, pneumonia is very different from pneumonia in younger patients and may be caused by unusual pathogens such as Haemophilus influenzae, Branhamella catarrhalis, or Mycobacterium tuberculosis. Conversely, an elderly person is unlikely to have pneumonia caused by Mycoplasma pneumoniae. Assessment of risk in the patient with pneumonia should include other factors. Cigarette smoking and use of alcohol are important factors to consider, for both increase the likelihood of gramnegative bacteria. Legionellosis is a regional problem; if it is a frequent cause of pneumonia in a particular community, erythromycin should be
included in empiric therapy for pneumonia in high-risk patients. Similarly, if AIDS is a problem in the community, a young male with pneumonia may require a different diagnostic and therapeutic approach than would otherwise be necessary. Assessment of risk in the patient with cholecystitis must also include age. Because the likelihood of bacteria colonizing gallstones increases with age, the elderly patient with acute cholecystitis should be treated with antimicrobics active against a broad spectrum of bacteria. For the same reason, the choice of prophylactic antimicrobics for elective cholecystectomy is also influenced by the patient's age. Parenteral antimicrobics can be utilized more effectively with proper assessment of risks. Some of the newer fl-lactam agents offer excellent empiric coverage for many pathogens, including Pseudomonas aeruginosa. These agents cost more than the combination of an earlier fl-lactam drug and an aminocyclitol but may be worth the increased cost if the patient has renal dysfunction or is old and is at higher risk for nephrotoxicity. Surgical patients pose their own risks. In early appendicitis (normal and acute appendicitis), one preoperative dose of a newer fl-lactam agent results in a very low rate ( - 3%) of postoperative infections. However, the postoperative infections of late appendicitis (gangrenous and perforated appendix) require 5 days of therapy with an agent, or agents, that have activity against both aerobic gram-negative bacilli and Bacteroidesfragilis. Thus, initial therapy in patients undergoing appendectomy consists of one preoperative dose; if a normal or
I,,[e,'tio~* Oi .......... ' Newsletter (ISSN 0278-2316i is issued monthly in one indexed Volume per year by l::isevier Science Publishing Co., I ..... 52 Vanderbih Av. . . . . New Y,,rk. NY
1(~17. Subscription price per year: institutions, $112.00: individuals, $56.00. For air mail to Europe, add $21.00; for air mail elsewherc, add $2400. Second-cla~,s po~,tage pending at New York. NY, and at additional mailing offices. Postmaster: Send address changes to Infectious Di.~eases Newsletter, Elsevier Science Publishing ('o.. Inc. 52 Vanderbilt Avenue. N e w York. NY 10017.
'~¢.1986 Elsevier SciencePublishingCo., Inc. 0278-2316/86/$0.00 + 2.20
35 Infectious Diseases Newsletter 5(5) May 1986 nonperforated, nongangrenous appendix is found at surgery, that is sufficient; if perforation and/or gangrene is found, 5 days of therapy will be necessary. Intraoperative flexibility is the key factor in the cost-effective use of antimicrobics in surgical patients; the duration (and perhaps choice of agent[s]) may be determined (after an initial preoperative dose) by what is found at surgery. Prophylactic use of antimicrobics for elective intraabdominal or pelvic surgery is rendered cost-effective by combining an intramuscular injection of an earlier cephalosporin (eg, cefazolin) with a perorally administered agent (eg, metronidazole or clindamycin) given as one dose preoperatively and one dose postoperatively. Intraoperative flexibility again is important; if an unanticipated problem (such as fecal spillage) occurs during the surgical procedure, the immediate and prolonged ( - 2 days) use of parenteral, broad-spectrum antimicrobics with aerobic and anaerobic activity is justified. Similarly, a compound fracture contaminated by dirt is justification for the prolonged use of antimicrobics providing antistaphylococcal and antipseudomonal activity. Elective bone and joint surgery, on the other hand, is well served by two intramuscular doses of an antistaphylococcal cephalosporin (eg, cefazolin). Prophylactic use of antimicrobics in cesarean sections should also be determined by risk factors such as premature rupture of the membranes. In summary, the rational use of antibacterial prophylaxis, when properly directed by assessment of risks and tempered by intraoperative flexibility, is one of the most important methods for cost-effective use of antimicrobics in surgical patients. Conversely, a standardized or "cookbook" approach will usually undertreat or overtreat the potential
infection, and hence not be costeffective.
Empiric Therapy Much of the use of antimicrobics is empiric and is based on a desire to achieve the broadest coverage and the greatest microbiologic activity possible. The practice of medicine founded on fear reflects the physician's concern for a severely ill patient with sepsis in whom the cause of the infection is unknown. It is also related to experience with immunosuppressed patients, where empiric therapy with broad-spectrum antimicrobics plays a prominent role. While the anxiety of the concerned physician for the septic patient is entirely appropriate, costeffective use of antimicrobics can still be achieved. Empiric therapy usually involves the use of a combination of antimicrobics; newer, more active agents; higher doses; or all of the preceding. Such empiric therapy is expensive. However, through logical evaluation of each patient, less expensive antimicrobic therapy is often possible. For example, neither clindamycin nor metronidazole may be needed for anaerobic coverage if the regimen already includes a fl-lactam agent with reasonable antianaerobic activity. Empiric therapy should also take into account epidemiologic factors; if legionellosis is not common in the community, the addition of erythromycin to the empiric therapy of pneumonia is not needed. Likewise, if methicillin-resistant Staphylococcus aureus is not a problem in a particular hospital, vancomycin is not needed. Finally, the use of amikacin is not necessary unless there is a local problem with aminocyclitol-resistant strains of gram-negative bacilli. Use of a single agent for empiric therapy enhances cost-effectiveness and is sufficient in most patients,
© 1986ElsevierSciencePublishing Co., Inc. 0278-2316/86/$0.00 + 2.20
reserving combinations of antimicrobics for immunosuppressed patients. There are newer fl-lactam agents now available that have a very broad spectrum of activity and cost-effectiveness when used as single agents. If a pathogen is isolated, a less expensive agent with specific activity against that organism may be substituted (eg, penicillin for Streptococcus pneumoniae ). Empiric therapy must always be evaluated with the aim of altering treatment after 2-3 days, when some of the excitement of the critical situation is over and laboratory data are available. Therapeutic reassessment is extremely important in the cost-effective use of antimicrobics and should be an integral part of empiric therapy.
Therapeutic Reassessment Physicians have always tended to select a regimen of antimicrobics for therapy (or prophylaxis) and then modify that regimen very little if the patient does well. However, early in therapy, as additional data become available, it is often possible to carry out cost-effective modification of the antimicrobial regimen. The results of Gram stains, cultures, and susceptibility tests may provide useful information about the pathogen(s) involved. Information about the excretion a n d / o r metabolism of the antimicrobic may be gleaned from studies of the function of the kidneys and the liver. Moreover, the response of the patient can be assessed. Acquiring these data over the first few days of empiric therapy may allow selection, from a number of alternative approaches, of one that is more cost-effective than the initial regimen. For example, one specific antimicrobic may be used on the basis of the results of cultures and susceptibility tests, with deletion of some or all of the ini-
36 Infectious Diseases Newsletter 5(5) May 1986 tially prescribed antimicrobics. In older patients, the total dose may be decreased a n d / o r the dosing interval increased. Once the patient has responded, other cost-effective changes are possible. Changing part or all of the therapy to less expensive parenteral agents, or to a perorally administrable agent, may be feasible. If the patient does not continue to respond favorably, the original regimen can be reinstituted while the patient is evaluated thoro u g h l y - - a far better course than randomly adding antimicrobics. Essential to wise therapy is frequent and habitual reassessment of antimicrobial regimens with possible application of cost-effective modifications in mind. New strategies for the cost-effective use of antimicrobics will allow the use of those antimicrobial agents that achieve optimal clinical results without imposing an unnecessary economic burden on the health care system. These strategies include at-
taining knowledge of antimicrobics, assessing risks in use, applying empiric therapy, and developing the habit of therapeutic reassessment. Understanding and use of these principles should enhance the cost-effective use of antimicrobics. Educational outreach programs must be utilized to foster learning and application of these strategies. Such programs are most often effective if clinicians are taught by clinician peers.
Bibliography Avorn J, Soumerai SB: Improving drug-therapy decisions through educational outreach: a randomized controlled trial of academically based "detailing." N Engl J Med 308:1457-1463, 1983. Eisenberg JM, Williams SV: Cost containment and changing physicians' practice behavior. Can the fox learn to guard the chicken coop? JAMA 246:2195-2201, 1981. Flynn NM: A plea for cost-containment
of antibiotics. Infect Dis Newsier 3:83-85, 1984. Lau WY, Fan ST, Chu KW, et al: Randomized, prospective, and double-blind trial of new fl-lactams in the treatment of appendicitis. Antimicrob Agents Chemother 28:639-642, 1985. Maugh TH II: A new wave of antibiotics builds. Science 214:1225-1228, 1981. McGowan JE Jr: Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Rev Infect Dis 5:1033-1048, 1983. McKellar PD: Treatment of community-acquired pneumonias. Am J Med 79(Suppl 2A):25-31, 1985. Murray PR, O'Bryne A: Cost of antibiotic therapy. N Engl J Med 308:226, 1983. Neu HC: Antimicrobial activity, bacterial resistance and antimicrobial pharmacology: is it possible to use new agents cost effectively? Am J Med 78(Suppl 6B):17-22, 1985. Schaf[ner WM, Ray WA, Federspiel CF, et al: Improving antibiotic prescribing in office practice: a controlled trial of three educational methods. JAMA 250:1728-1732, 1983.
CASE REPORTS
Case 1 A 64-year-old Filipino woman came to the emergency room with a 4-hour history of bloody diarrhea that had begun abruptly. She also complained of nausea, vomiting, and tightness of her chest. About 1 hour before onset of illness, she had consumed a meal of freeze-dried oysters and fish stew. Earlier in the day, she had eaten tuna casserole served at a senior citizens' home; no other persons who partook of the casserole became ill. On admission, she had no fever, but had orthostatic hyp'otension and diffuse abdominal tenderness. Rectal examination produced bright red blood, and proctoscopy yielded foul-smelling material with liquid feces. There were 12,100 leuko-
cytes//~l of peripheral blood with 45% mature and 5% band neutrophils, 44% lymphocytes and 6% monocytes. The hematocrit was 42.7%, falling to 35.4% with hydration. The potassium was 2.7 m E q / L . In addition to blood and mucus, the feces contained polymorphonuclear leukocytes, but neither ova, protozoa, nor worms. Cultures yielded Plesiomonas shigelloides and no other bacterial pathogens. By testing in vitro, the P. shigelloides was susceptible to tetracycline, chloramphenicol, cephalothin, amikacin, gentamicin, tobramycin, and trimethoprim-sulfamethoxazole; it was resistant to ampicillin and carbenicillin. Without specific therapy, the feces became guaiac negative within 24 hours of admission. The diarrhea ~51986 ElsevierSciencePublishing Co., Inc. 0278-2316/86/$0.00 + 2.20
gradually subsided, and she was discharged symptom free after 3 days. Case 2 A 40-year-old man came to the emergency room because of diarrhea and lower abdominal pain of 3 days' duration. The diarrhea began shortly after his return from a trip to Panama, and was associated with crampy abdominal pain after 24 hours, and nausea and vomiting on the day of admission. He was admitted because the pain was referred to the right lower quadrant of the abdomen. Aside from a temperature of 99.8°F and fight lower quadrant tenderness without rebound, the physical examination was unremarkable.
Editor
Paul D. Hoeprich, MD Division of Infectious and Immunologic Diseases University of California, Davis Medical Center
Associate Editors
R u t h M. Lawrence, MD
Larry K. Picketing, MD
Charles W. Stratton, MD
Division of Infectious Diseases Texas Tech University Health Sciences Center
Program in Infectious Diseases and Clinical Microbiology The University of Texas Medical School at Houston
Department of Pathology Vanderbilt University Medical Center
New Strategies for the Cost-effective Use of Antimicrobics Charles W. Stratton, MD
()lllcll[!
New Strategies for the Cost-effective Use of Antimicrobics Charles W. Stratton CASE REPORT Sanford H. Robbins, Sally Calzada, and John Keiser
33
36
COMMENTS ON CURRENT PUBLICATIONS
Elsevier 0278-2316/86/$0.00 + 2.20
37
Vanderbilt University School of Medicine, Nashville, Tennessee
Medical practice in the 1980s is caught between advances in pharmaceutical agents and the demand for accountability. The introduction of new antimicrobics that are very costly, in comparison with older agents, has greatly complicated antimicrobial therapy. It is now possible to use antimicrobics correctly in a therapeutic sense, but to misuse them in an economic sense, by prescribing a more expensive agent when a less expensive agent would suffice. Nonetheless, recognition of new pathogens, increasing resistance of pathogens to older antimicrobics, and more complicated clinical problems have increased the need for the new agents. It is difficult for physicians not specializing in infectious diseases to keep abreast of changes in the triad of patients, pathogens, and antimicrobics. These changes, along with the recent emphasis on controlling
costs, argue for new strategies in the use of antimicrobics. Such strategies promise to be useful in controlling costs, when combined with an educational outreach program.
Familiarization Clinicians who prescribe antimicrobics need to invest time and energy beyond reading a package insert to gain familiarity with antimicrobial agents. For example, the dosing interval on the package insert may reflect the way the antimicrobic was studied, but does not necessarily represent the actual pharmacokinetics of the drug. Table 1 provides data regarding some commonly used antimicrobics that are often dosed more frequently than needed. The age of the patient may be important. The dosing of aminocyclitols was originally based on the pharmacokinetics of these drugs in young adults. However, when treat-
ISSN 0278-2316
IDINDN 5(5)33-40. 1986
34 Infectious Diseases Newsletter 5(5) May 1986 Table 1. Pharmacokinetics of Commonly Used Antimicrobics
Antimicrobic
Half-life in hours
Tetracycline Sulfamethoxazole Trimethoprim Vancomyein~ Metronidazole Amphotericin B"
6-12 8-10 10-12 ) 6- 9 6-10 24-48
Dosage interval in hours Conventional Pharmacologic 6
12
6 6 6 24
12 12 12 48
"Doses doubled when interval is doubled.
ing older patients who often have decreased renal function or diminished renal reserve, it may be safer to divide the total daily dose by two instead of three, giving a larger dose every 12 hours. This will result in higher peak levels (6-8 ~ g / m l for gentamicin and tobramycin) and lower trough levels. Lack of familiarity may mean that a newer agent with an advantage for a particular infection either is not used or is used incorrectly. The increased tissue penetration of the newer cephalosporins is a factor favoring their use in many kinds of bacterial meningitis and in pneumonias. Knowledge of the clinical results with the newer antipseudomonal fl-lactam agents leads to the conclusion that aminocyclitols must still be included in the treatment of serious pseudomonal infections. Glib labeling as to "generation" has in part contributed to inadequacy of understanding. The newer cephalosporins are quite diverse in spectrum, activity, and pharmacokinetic properties. The use of the terms "second-generation cephalosporin" or "third-generation cephalosporin" implies a similarity that simply does not exist. Antimicrobics must be thought of as drugs --individual agents that are chem-
ical entities--and not lumped as a "generation." To be familiar with an antimicrobic is to know its (1) spectrum of activity; (2) mechanism of action; (3) proven clinical efficacy; (4) pharmacokinetic properties; (5) side effects; and (6) cost. Assessment of Risk
There is need for improved assessment of risk in the use of antimicrobics for prophylaxis and treatment. Pneumonia in an adult cannot be treated without consideration of the patient's age. In the elderly, pneumonia is very different from pneumonia in younger patients and may be caused by unusual pathogens such as Haemophilus influenzae, Branhamella catarrhalis, or Mycobacterium tuberculosis. Conversely, an elderly person is unlikely to have pneumonia caused by Mycoplasma pneumoniae. Assessment of risk in the patient with pneumonia should include other factors. Cigarette smoking and use of alcohol are important factors to consider, for both increase the likelihood of gramnegative bacteria. Legionellosis is a regional problem; if it is a frequent cause of pneumonia in a particular community, erythromycin should be
included in empiric therapy for pneumonia in high-risk patients. Similarly, if AIDS is a problem in the community, a young male with pneumonia may require a different diagnostic and therapeutic approach than would otherwise be necessary. Assessment of risk in the patient with cholecystitis must also include age. Because the likelihood of bacteria colonizing gallstones increases with age, the elderly patient with acute cholecystitis should be treated with antimicrobics active against a broad spectrum of bacteria. For the same reason, the choice of prophylactic antimicrobics for elective cholecystectomy is also influenced by the patient's age. Parenteral antimicrobics can be utilized more effectively with proper assessment of risks. Some of the newer fl-lactam agents offer excellent empiric coverage for many pathogens, including Pseudomonas aeruginosa. These agents cost more than the combination of an earlier fl-lactam drug and an aminocyclitol but may be worth the increased cost if the patient has renal dysfunction or is old and is at higher risk for nephrotoxicity. Surgical patients pose their own risks. In early appendicitis (normal and acute appendicitis), one preoperative dose of a newer fl-lactam agent results in a very low rate ( - 3%) of postoperative infections. However, the postoperative infections of late appendicitis (gangrenous and perforated appendix) require 5 days of therapy with an agent, or agents, that have activity against both aerobic gram-negative bacilli and Bacteroidesfragilis. Thus, initial therapy in patients undergoing appendectomy consists of one preoperative dose; if a normal or
I,,[e,'tio~* Oi .......... ' Newsletter (ISSN 0278-2316i is issued monthly in one indexed Volume per year by l::isevier Science Publishing Co., I ..... 52 Vanderbih Av. . . . . New Y,,rk. NY
1(~17. Subscription price per year: institutions, $112.00: individuals, $56.00. For air mail to Europe, add $21.00; for air mail elsewherc, add $2400. Second-cla~,s po~,tage pending at New York. NY, and at additional mailing offices. Postmaster: Send address changes to Infectious Di.~eases Newsletter, Elsevier Science Publishing ('o.. Inc. 52 Vanderbilt Avenue. N e w York. NY 10017.
'~¢.1986 Elsevier SciencePublishingCo., Inc. 0278-2316/86/$0.00 + 2.20
35 Infectious Diseases Newsletter 5(5) May 1986 nonperforated, nongangrenous appendix is found at surgery, that is sufficient; if perforation and/or gangrene is found, 5 days of therapy will be necessary. Intraoperative flexibility is the key factor in the cost-effective use of antimicrobics in surgical patients; the duration (and perhaps choice of agent[s]) may be determined (after an initial preoperative dose) by what is found at surgery. Prophylactic use of antimicrobics for elective intraabdominal or pelvic surgery is rendered cost-effective by combining an intramuscular injection of an earlier cephalosporin (eg, cefazolin) with a perorally administered agent (eg, metronidazole or clindamycin) given as one dose preoperatively and one dose postoperatively. Intraoperative flexibility again is important; if an unanticipated problem (such as fecal spillage) occurs during the surgical procedure, the immediate and prolonged ( - 2 days) use of parenteral, broad-spectrum antimicrobics with aerobic and anaerobic activity is justified. Similarly, a compound fracture contaminated by dirt is justification for the prolonged use of antimicrobics providing antistaphylococcal and antipseudomonal activity. Elective bone and joint surgery, on the other hand, is well served by two intramuscular doses of an antistaphylococcal cephalosporin (eg, cefazolin). Prophylactic use of antimicrobics in cesarean sections should also be determined by risk factors such as premature rupture of the membranes. In summary, the rational use of antibacterial prophylaxis, when properly directed by assessment of risks and tempered by intraoperative flexibility, is one of the most important methods for cost-effective use of antimicrobics in surgical patients. Conversely, a standardized or "cookbook" approach will usually undertreat or overtreat the potential
infection, and hence not be costeffective.
Empiric Therapy Much of the use of antimicrobics is empiric and is based on a desire to achieve the broadest coverage and the greatest microbiologic activity possible. The practice of medicine founded on fear reflects the physician's concern for a severely ill patient with sepsis in whom the cause of the infection is unknown. It is also related to experience with immunosuppressed patients, where empiric therapy with broad-spectrum antimicrobics plays a prominent role. While the anxiety of the concerned physician for the septic patient is entirely appropriate, costeffective use of antimicrobics can still be achieved. Empiric therapy usually involves the use of a combination of antimicrobics; newer, more active agents; higher doses; or all of the preceding. Such empiric therapy is expensive. However, through logical evaluation of each patient, less expensive antimicrobic therapy is often possible. For example, neither clindamycin nor metronidazole may be needed for anaerobic coverage if the regimen already includes a fl-lactam agent with reasonable antianaerobic activity. Empiric therapy should also take into account epidemiologic factors; if legionellosis is not common in the community, the addition of erythromycin to the empiric therapy of pneumonia is not needed. Likewise, if methicillin-resistant Staphylococcus aureus is not a problem in a particular hospital, vancomycin is not needed. Finally, the use of amikacin is not necessary unless there is a local problem with aminocyclitol-resistant strains of gram-negative bacilli. Use of a single agent for empiric therapy enhances cost-effectiveness and is sufficient in most patients,
© 1986ElsevierSciencePublishing Co., Inc. 0278-2316/86/$0.00 + 2.20
reserving combinations of antimicrobics for immunosuppressed patients. There are newer fl-lactam agents now available that have a very broad spectrum of activity and cost-effectiveness when used as single agents. If a pathogen is isolated, a less expensive agent with specific activity against that organism may be substituted (eg, penicillin for Streptococcus pneumoniae ). Empiric therapy must always be evaluated with the aim of altering treatment after 2-3 days, when some of the excitement of the critical situation is over and laboratory data are available. Therapeutic reassessment is extremely important in the cost-effective use of antimicrobics and should be an integral part of empiric therapy.
Therapeutic Reassessment Physicians have always tended to select a regimen of antimicrobics for therapy (or prophylaxis) and then modify that regimen very little if the patient does well. However, early in therapy, as additional data become available, it is often possible to carry out cost-effective modification of the antimicrobial regimen. The results of Gram stains, cultures, and susceptibility tests may provide useful information about the pathogen(s) involved. Information about the excretion a n d / o r metabolism of the antimicrobic may be gleaned from studies of the function of the kidneys and the liver. Moreover, the response of the patient can be assessed. Acquiring these data over the first few days of empiric therapy may allow selection, from a number of alternative approaches, of one that is more cost-effective than the initial regimen. For example, one specific antimicrobic may be used on the basis of the results of cultures and susceptibility tests, with deletion of some or all of the ini-
36 Infectious Diseases Newsletter 5(5) May 1986 tially prescribed antimicrobics. In older patients, the total dose may be decreased a n d / o r the dosing interval increased. Once the patient has responded, other cost-effective changes are possible. Changing part or all of the therapy to less expensive parenteral agents, or to a perorally administrable agent, may be feasible. If the patient does not continue to respond favorably, the original regimen can be reinstituted while the patient is evaluated thoro u g h l y - - a far better course than randomly adding antimicrobics. Essential to wise therapy is frequent and habitual reassessment of antimicrobial regimens with possible application of cost-effective modifications in mind. New strategies for the cost-effective use of antimicrobics will allow the use of those antimicrobial agents that achieve optimal clinical results without imposing an unnecessary economic burden on the health care system. These strategies include at-
taining knowledge of antimicrobics, assessing risks in use, applying empiric therapy, and developing the habit of therapeutic reassessment. Understanding and use of these principles should enhance the cost-effective use of antimicrobics. Educational outreach programs must be utilized to foster learning and application of these strategies. Such programs are most often effective if clinicians are taught by clinician peers.
Bibliography Avorn J, Soumerai SB: Improving drug-therapy decisions through educational outreach: a randomized controlled trial of academically based "detailing." N Engl J Med 308:1457-1463, 1983. Eisenberg JM, Williams SV: Cost containment and changing physicians' practice behavior. Can the fox learn to guard the chicken coop? JAMA 246:2195-2201, 1981. Flynn NM: A plea for cost-containment
of antibiotics. Infect Dis Newsier 3:83-85, 1984. Lau WY, Fan ST, Chu KW, et al: Randomized, prospective, and double-blind trial of new fl-lactams in the treatment of appendicitis. Antimicrob Agents Chemother 28:639-642, 1985. Maugh TH II: A new wave of antibiotics builds. Science 214:1225-1228, 1981. McGowan JE Jr: Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Rev Infect Dis 5:1033-1048, 1983. McKellar PD: Treatment of community-acquired pneumonias. Am J Med 79(Suppl 2A):25-31, 1985. Murray PR, O'Bryne A: Cost of antibiotic therapy. N Engl J Med 308:226, 1983. Neu HC: Antimicrobial activity, bacterial resistance and antimicrobial pharmacology: is it possible to use new agents cost effectively? Am J Med 78(Suppl 6B):17-22, 1985. Schaf[ner WM, Ray WA, Federspiel CF, et al: Improving antibiotic prescribing in office practice: a controlled trial of three educational methods. JAMA 250:1728-1732, 1983.
CASE REPORTS
Case 1 A 64-year-old Filipino woman came to the emergency room with a 4-hour history of bloody diarrhea that had begun abruptly. She also complained of nausea, vomiting, and tightness of her chest. About 1 hour before onset of illness, she had consumed a meal of freeze-dried oysters and fish stew. Earlier in the day, she had eaten tuna casserole served at a senior citizens' home; no other persons who partook of the casserole became ill. On admission, she had no fever, but had orthostatic hyp'otension and diffuse abdominal tenderness. Rectal examination produced bright red blood, and proctoscopy yielded foul-smelling material with liquid feces. There were 12,100 leuko-
cytes//~l of peripheral blood with 45% mature and 5% band neutrophils, 44% lymphocytes and 6% monocytes. The hematocrit was 42.7%, falling to 35.4% with hydration. The potassium was 2.7 m E q / L . In addition to blood and mucus, the feces contained polymorphonuclear leukocytes, but neither ova, protozoa, nor worms. Cultures yielded Plesiomonas shigelloides and no other bacterial pathogens. By testing in vitro, the P. shigelloides was susceptible to tetracycline, chloramphenicol, cephalothin, amikacin, gentamicin, tobramycin, and trimethoprim-sulfamethoxazole; it was resistant to ampicillin and carbenicillin. Without specific therapy, the feces became guaiac negative within 24 hours of admission. The diarrhea ~51986 ElsevierSciencePublishing Co., Inc. 0278-2316/86/$0.00 + 2.20
gradually subsided, and she was discharged symptom free after 3 days. Case 2 A 40-year-old man came to the emergency room because of diarrhea and lower abdominal pain of 3 days' duration. The diarrhea began shortly after his return from a trip to Panama, and was associated with crampy abdominal pain after 24 hours, and nausea and vomiting on the day of admission. He was admitted because the pain was referred to the right lower quadrant of the abdomen. Aside from a temperature of 99.8°F and fight lower quadrant tenderness without rebound, the physical examination was unremarkable.