Pediatric Annals

ANTIBIOTICS FOR THE PEDIATRICIAN 

Principles of Antibiotic Use for the Treatment of Bacterial Infection

James K Todd, MD

Abstract

Prscription of antibiotics in the inpatient setmay be the single largest expense on the spital formulary. In addition, the frequency of antibiotic use in the hospital and the proximity of patients to each other may be a major impetus for the emergence and spread of antimicrobial resistance. Consequently, the inpatient setting represents one of the greatest opportunities to control the emergence of resistance by the application of evidence-based antimicrobial use principles.

We commonly talk about limiting the use of antibiotics in the hospital setting to decrease costs, to reduce the potential for adverse reactions, and to diminish the propensity to select for resistant organisms.1"4 These are valid epidemiologie goals that, to many physicians, are important for the overall hospital population, but not for the individual patient. Clinicians often resist guidelines that limit antibiotic therapy because of their concern for the vulnerability of compromised patients who may be at high risk for rapid deterioration with bacterial infection. However, recent studies have shown that the use of computer-assisted antibiotic guidelines5'6 and rapid culture and susceptibility testing techniques7 may actually reduce costs while improving individual patient care. To ensure the availability of effective antimicrobial options in the future,8 we all must apply evidence-based principles of antibiotic use to our current patients with the confidence that such practice ensures good care for the present as well as the future.

CATEGORIES OF ANTIBIOTIC USE IN THE HOSPITAL SETTING

The three major reasons for antimicrobial prescription are treatment of a known infection, presumptive treatment of a suspected infection, and prophylactic treatment to prevent the development of infection. In many hospitals, each of these categories of antibiotic treatment comprises approximately one-third of all treatment courses.9 As shown in Table 1, for each major category of antibiotic treatment, there are four major questions that need to be answered to ensure appropriate drug use:

1. When to start?

2. What to start?

3. When to modify therapy?

4. When to stop?

For patients with proven infection, antibiotics appropriate for the clinical condition and organism are started in the presence of convincing clinical or culture evidence of need, and therapy is discontinued on completion of an appropriate antibiotic course. Just as commonly, other patients are given presumptive antibiotic treatment for a possible infection while awaiting the results of further testing. This is often referred to as the "rule out sepsis" approach and is frequently employed in the neonatal unit the intensive care unit, and the oncology unit. The presumption is that such patients are at a high risk of rapid deterioration, and that antibiotic therapy will "cover" them until further studies identify the true cause of their symptoms. Such therapy is then modified based on culture results or stopped if culture results are negative. Unfortunately, in many patients, the proper cultures are never done, but therapy is continued because of continued diagnostic uncertainty or because many physicians hope that such therapy might prevent subsequent infection.

Table

The third reason for giving combinations of antibiotics is to reduce the emergence of resistance. This is especially important in the treatment of tuberculosis. Finally, combinations of the antibiotics may be useful in certain cases where synergy permits the use of lower concentrations of a particular toxic antibiotic (eg, amphotericin and 5-flucytosine in fungal meningitis).

For the most part, antibiotic combinations will be given as presumptive therapy in high-risk patients and should be modified as soon as the proper cultures, taken prior to the initiation of therapy, identify the true causative agent.

ANTIBIOTIC PROPHYLAXIS

The concept of antibiotic prophylaxis has been widely studied. Physicians often talk of "covering their patients" with antibiotics in an…

Prscription of antibiotics in the inpatient setmay be the single largest expense on the spital formulary. In addition, the frequency of antibiotic use in the hospital and the proximity of patients to each other may be a major impetus for the emergence and spread of antimicrobial resistance. Consequently, the inpatient setting represents one of the greatest opportunities to control the emergence of resistance by the application of evidence-based antimicrobial use principles.

We commonly talk about limiting the use of antibiotics in the hospital setting to decrease costs, to reduce the potential for adverse reactions, and to diminish the propensity to select for resistant organisms.1"4 These are valid epidemiologie goals that, to many physicians, are important for the overall hospital population, but not for the individual patient. Clinicians often resist guidelines that limit antibiotic therapy because of their concern for the vulnerability of compromised patients who may be at high risk for rapid deterioration with bacterial infection. However, recent studies have shown that the use of computer-assisted antibiotic guidelines5'6 and rapid culture and susceptibility testing techniques7 may actually reduce costs while improving individual patient care. To ensure the availability of effective antimicrobial options in the future,8 we all must apply evidence-based principles of antibiotic use to our current patients with the confidence that such practice ensures good care for the present as well as the future.

CATEGORIES OF ANTIBIOTIC USE IN THE HOSPITAL SETTING

The three major reasons for antimicrobial prescription are treatment of a known infection, presumptive treatment of a suspected infection, and prophylactic treatment to prevent the development of infection. In many hospitals, each of these categories of antibiotic treatment comprises approximately one-third of all treatment courses.9 As shown in Table 1, for each major category of antibiotic treatment, there are four major questions that need to be answered to ensure appropriate drug use:

1. When to start?

2. What to start?

3. When to modify therapy?

4. When to stop?

For patients with proven infection, antibiotics appropriate for the clinical condition and organism are started in the presence of convincing clinical or culture evidence of need, and therapy is discontinued on completion of an appropriate antibiotic course. Just as commonly, other patients are given presumptive antibiotic treatment for a possible infection while awaiting the results of further testing. This is often referred to as the "rule out sepsis" approach and is frequently employed in the neonatal unit the intensive care unit, and the oncology unit. The presumption is that such patients are at a high risk of rapid deterioration, and that antibiotic therapy will "cover" them until further studies identify the true cause of their symptoms. Such therapy is then modified based on culture results or stopped if culture results are negative. Unfortunately, in many patients, the proper cultures are never done, but therapy is continued because of continued diagnostic uncertainty or because many physicians hope that such therapy might prevent subsequent infection.

Table

TABLE 1Principles for Starting, Modifying, and Stopping Antibiotic Therapy for Hospital lnpatients

TABLE 1

Principles for Starting, Modifying, and Stopping Antibiotic Therapy for Hospital lnpatients

During the past 20 years it has become well established that intraoperative prophylactic antibiotics, if given during contaminated surgical procedures, can significantly reduce the rate of surgical wound infection. The antibiotics selected are chosen based on the organism that is likely to be encountered at that surgical site. Many studies have shown that a single dose that reaches therapeutic levels during the surgical procedure is sufficient to provide maximum benefit.10'11 Major surgical organizations recommend that prophylactic antibiotics given for such a purpose be continued for no longer than 1 day. Unfortunately, many surgeons intuitively continue the antibiotics for longer periods of time. When such patients ultimately do become infected, it is often with very resistant organisms - the very problem we hope to minimize.

THE POTENTIAL FOR REDUCTION IN ANTIBIOTIC USE

Based on the three categories in Table 1, it is estimated that total antibiotic use in the hospital could be reduced by 25% or more by simply adhering to evidence-based prescription guidelines. Figure IA shows the cumulative antibiotic exposure of a typical cohort given antibiotics if the guidelines in Table 1 are followed, assuming a 7- to 10-day treatment course for those patients with proven infection. Figure IB shows the same analysis for a similar cohort if antibiotic guidelines are not followed. The difference between the two scenarios represents an overall reduction of 25% in total antibiotic days when prescription guidelines are followed. For example, in a neonatal intensive care unit, we showed the potential for a reduction of almost 40% in antibiotic use if antibiotics were stopped based on a rigorous diagnostic evaluation process.12 Importantly, there may also be a commensurate reduction in adverse évente for individual patients, and, presumably, a reduced potential for the development and transmission of antimicrobial resistance. In fact, a number of studies have confirmed that adherence to evidence-based guidelines can result in significantly improved patient outcomes.5,12,13

Figure 1 . (A) Cumulative daily antibiotic exposure of a typical cohort given antibiotics if antibiotic guidelines are followed: 33% proven infections treated for 7-10 days, 33% presumptive infections treated for 48 hours until culture results are negative (antibiotics stopped in 80%, continued in 20%), and 33% given prophylactic antibiotics that were discontinued that same day. (B) Cumulative daily antibiotic exposure of a typical cohort given antibiotics if antibiotic guidelines are noi followed: 33% proven infections treated for 7-10 days, 33% presumptive infections treated for 48 hours until culture results are negative (antibiotics gradually discontinued without much regard for culture results or cultures not taken), and 33% given prophylactic antibiotics that were discontinued gradually over many days.

Figure 1 . (A) Cumulative daily antibiotic exposure of a typical cohort given antibiotics if antibiotic guidelines are followed: 33% proven infections treated for 7-10 days, 33% presumptive infections treated for 48 hours until culture results are negative (antibiotics stopped in 80%, continued in 20%), and 33% given prophylactic antibiotics that were discontinued that same day. (B) Cumulative daily antibiotic exposure of a typical cohort given antibiotics if antibiotic guidelines are noi followed: 33% proven infections treated for 7-10 days, 33% presumptive infections treated for 48 hours until culture results are negative (antibiotics gradually discontinued without much regard for culture results or cultures not taken), and 33% given prophylactic antibiotics that were discontinued gradually over many days.

THE APPROPRIATE WORKUP

What is the appropriate workup for inpatients suspected to have bacterial infection? We often talk about a "rule out sepsis" evaluation and only do a blood culture. Even in the newborn nursery, we found that only half of those patients with proven bacterial infection (ie, those requiring antibiotic treatment) had a positive result on blood cuiture. This emphasizes that sepsis does not necessarily imply bacteremia!12 If we are to follow the guidelines in Table 1, it is critically important to obtain proper cultures and other diagnostic material from patients prior to initiating antimicrobial therapy. This is especially true in patients who have compromised host defenses, those with severe illness, those who have failed prior antimicrobial therapy, and those who will be given multiple antimicrobial agents (Table 2). If these cultures identify the causative agent, therapy can be narrowed or optimized according to susceptibility results.

What are the proper cultures? The basic principle is to follow the advice of the notorious bank robber Willie Sutton, who said to always "go where the money is."14 Applied to the diagnosis of serious bacterial diseases, the advice is "culture where the infection is!" We are rarely squeamish about doing a spinal tap (ie, sticking a needle in the lumbar spinal space) in a child who might have bacterial meningitis, and should be no more deterred about sticking a needle into most other infected sites or obtaining an uncontamrnated culture by some other method. The technique is simple15 and provides isolates for antimicrobial susceptibility testing that let us know how to modify antibiotics and when to stop them. When we start antibiotics, we should always know the answer to the question, "How will I know when to stop?" (Example A).

Table

TABLE 2Steps In Decision Making for the Use of Pa renteral Antimicrobial Agents

TABLE 2

Steps In Decision Making for the Use of Pa renteral Antimicrobial Agents

Figure 2. Definition of "susceptible," "intermediate," and "resistant" by comparison of organism minimal inhibitory concentrations (MICs) with achievable antibiotic blood levels. (MICs and levels may vary depending on organism and antibiotic.)

Figure 2. Definition of "susceptible," "intermediate," and "resistant" by comparison of organism minimal inhibitory concentrations (MICs) with achievable antibiotic blood levels. (MICs and levels may vary depending on organism and antibiotic.)

Example A: A newborn has been treated with ampicillin and gentamicin for 2 days for symptomatic pneumonia confirmed on x-ray. The results of the following tests are negative: blood culture, cerebrospinal fluid culture, stool culture, gastric aspirate culture, throat culture, and group B streptococcus antigen. Can antibiotics be stopped?

Answer It is not clear. Blood cultures may be negative in the presence of bacterial infection up to 50% of the time. Group B streptococcus is by no means the only cause of early-onset pneumonia, sepsis, or both. A trachéal aspirate prior to starting antibiotics would have been the only way to rule out infection with confidence. Because of this uncertainty, antibiotics are often continued (unnecessarily).

The answer will be dear only when we obtain the proper cultures and tests before starting treatment, particularly in patients with serious infections, after failure of prior treatment, in hosts with compromised immune systems, and, especially, if empiric treatment includes broad-spectrum antibiotics or multiple antibiotics.

ANTIMICROBIAL SUSCEPTIBILITY TESTING

Antimicrobial susceptibility testing requires more than putting a few antibiotic discs on an agar plate. To get interpretable results, this test should be done only in a laboratory using carefully defined procedures (National Committee for Clinical Laboratory Standards). The use of nonstandard media, inoculum size, or growth conditions may give markedly different and undependable results. There are several different ways to test antimicrobial susceptibility. (1) Identification of an antibiotic-destroying enzyme (ß-lactamase) implies resistance to that class of antimicrobial agents. (2) Microtiter broth dilution techniques or the new "?-test" can be used to determine the minimal inhibitory concentration (MIC) of that antibiotic for the tested organism, which is the amount of antibiotic necessary to inhibit the organism under carefully controlled laboratory conditions. (3) Disc diffusion tests can be done on certain organisms to estimate the MIC. In each case, an accredited laboratory should select the methodology known to be appropriate for each organism. It is important to recognize, in fact, that some organisms do not have reliable guidelines for susceptibility interpretation, forcing us to rely on published clinical experience.

Knowing the MIC is not enough. The laboratory's standards also require an understanding of the clinical pharmacology of each antimicrobial agent to infer antibiotic susceptibility. As shown in Figure 2, if the laboratory says an organism is "susceptible," it means the MIC is less than the antibiotic concentration achievable in the patient's blood and soft tissue using appropriate antibiotic dosages. "Resistant" implies that the MIC is higher than such levels.

It should be emphasized that laboratory personnel do not know the patient as well as the clinician does. They perform susceptibility testing in special media, at a pH of 7.2, at a known inoculum size. Nevertheless, the laboratory's conclusion that the organism is "resistant" or "susceptible," even by its rigorous standards, is not enough. It is well known that some antibiotics (eg, the aminoglycosides) do not work well at lower pHs or higher inoculum sizes. As shown in Figure 2, die treating physician must therefore factor in an understanding of the circumstances of the infection (a different application of Sutton's law) in the context of that particular patient to augment the information provided by the laboratory. For example, antibiotics are often at much lower levels in sequestered sites of infection (eg, brain, bone, or abscess) than the blood levels used by the laboratory to determine susceptibility. In contrast, levels may be higher in the urine. As shown in Figure 2, both organisms 1 and 2 would be called "susceptible" by the laboratory, but only organism 1 would have a MIC low enough to be adequately treated by antibiotic levels achievable in the cerebrospinal fluid. Organism 3 falls in the "intermediate" range where successful treatment with that antibiotic might be questionable. With organism 4, success would be unlikely unless the infection were at a site where higher than usual antibiotic levels (eg, urine) could be attained. Below are additional examples (B-E) of the importance of clinical interpretation of laboratory susceptibility results.

Example B: A 2-week-old boy has meningitis caused by Escherichia coli that the laboratory says has a "susceptible" MIC to gentamicin. Despite treatment with gentamicin in appropriate doses, a second spinal fluid sample also grows E. coli. Give several possible explanations.

Answer:

1. What the laboratory means when it says "susceptible" is that the organism has a MIC less than the level of the antibiotic that can usually be achieved in the blood. Antibiotic penetration into the spinal fluid is usually much less than blood levels, so although the organism is "susceptible," there may be insufficient antibiotic in the spinal fluid to treat it.

2. Antibiotic susceptibility testing in the laboratory is done at a pH of 7.2. The pH of infected spinal fluid may be more acidic and gentamicin does not work well at a lower pH.

3. The initial population of the E. coli may have been mixed and the gentamicin treatment selected out a resistant strain.

Example C: A 3-year-old girl has a urinary tract infection caused by E. coli successfully treated with ampicillin despite the fact that the laboratory says it is "resistant." Why? Answer: The laboratory means that the organism is resistant to levels of antibiotic that can be achieved in the blood. However, ampicillin is excreted in the urine, resulting in higher levels that were, in mis case, sufficient to kill the organism.

Example D: The same girl as in example C gets pyelonephritis with an Enterobacier species that is "susceptible" to tobramycin. Two days later her urine culture still grows the organism despite this treatment. Why?

Answer: Aminoglycoside antibiotics do not work well at the low urine pH commonly seen in patients with urinary tract infection. Alkalinizing the urine may help.

Example E: A 10-year-old boy with leukemia undergoing vigorous chemotherapy has Pseudomonas aeruginosa sepsis. His fever goes away with appropriate twodrug, bactericidal therapy, but he experiences a relapse when therapy is stopped. Why?

Answer Antibiotics on their own may not be sufficient treatment for serious infections in patients with compromised host defenses. This patient had a persistently low neutrophil count, which was insufficient to assist in the complete eradication of this organism.

Thus, antimicrobial susceptibility testing, although an important part of therapeutic decision making, involves assumptions mat the clinician must understand, especially for treatment of patients with serious infections.

Ultimately, the true test of the efficacy of therapy is patient response. Antimicrobial therapy cannot be expected to cure every infection (eg, abscess or patients with compromised host defenses) unless additional supportive treatment (eg, drainage or neutrophil enhancement) is undertaken. Patients who do not respond to seemingly appropriate therapy may require reassessment, including reculturing and repeat susceptibility testing, to determine whether resistant strains of the organism or superinfection with a resistant organism is present. Some antibiotics are only marginally effective against certain organisms, and many deep tissue infections require surgical drainage procedures as an adjunct to antimicrobial therapy.

Figure 3. Approach for the treatment of bacterial infections based on severity and complexity of illness.

Figure 3. Approach for the treatment of bacterial infections based on severity and complexity of illness.

APPROACH FOR PRESUMPTIVE ANTIBIOTIC USE IN HOSPITALIZED PATIENTS

The steps in diagnosis and treatment of serious bacterial infections are shown in Table 2. Accurate clinical diagnosis of the suspected site of infection - based on the history, physical examination, and initial laboratory tests - leads to the appropriate consideration of common organisms usually associated with such infections and their probable patterns of susceptibility to antimicrobial agente.16 After obtaining cultures to identify the precise cause of the infection, it is appropriate to initiate empirical antimicrobial therapy, taking into account the above considerations as well as a knowledge of regimens that have proved successful in the past. Therapy is modified according to patient response and culture results.

Table

TABLE 3Steps In Switching From Parenteral to Oral Therapy for an Initially Serious Infection

TABLE 3

Steps In Switching From Parenteral to Oral Therapy for an Initially Serious Infection

Important considerations include the age of the child, the presence of any host defense deficiencies, a thorough understanding of unusual exposures, and the severity of the child's illness. Children who are severely ill (eg, suspected meningitis) or who have infections known to progress rapidly to more severe illness (eg, bacteremia) should be evaluated quickly, hospitalized, and treated expeditiously with broad antimicrobial coverage until culture results allow a narrowing of therapy. As shown in Figure 3, patiente with a milder illness, suspected to be caused by organisms with predictable susceptibilities, may be treated empirically with a single agent administered orally. If that initial therapy fails, a more extensive workup is then considered.

CHANGING TO ORAL THERAPY

In patients initially treated with parenteral therapy, it is often desirable to change to oral therapy once symptoms are improving and the causative agent is identified. Although home intravenous therapy is now commonly used, an oral option is often possible if certain criteria are met (Table 3). Such a change in therapy cannot be made unless an oral agent that results in sufficient blood levels is available, the causative organism and its susceptibility patterns are known or can be inferred from the response to single-agent parenteral therapy compliance with administration of an oral antibiotic can be anticipated, and appropriate blood levels can be inferred by either (1) the pharmacology of the drug, (2) the measurement of blood levels, or (3) the measurement of serum killing powers. It is important to recognize that these principles are merely guidelines. The only accurate measure of the success of antimicrobial therapy is the response of the patient.

Table

TABLE 4Principles for the Use of Antibiotic Combinations

TABLE 4

Principles for the Use of Antibiotic Combinations

ANTIBIOTIC COMBINATIONS

Antibiotic combinations are often used in high-risk patients for presumptive treatment. As shown in Table 4, there are four main reasons for giving antibiotic combinations. The most common is the attempt to use multiple antibiotics to give broad coverage in patients who have compromised host defenses and could be infected with a wide variety of organisms. In theory, this broad coverage is intended to be continued only until such time that appropriate cultures define the source and the cause of infection.17 However, many physicians do not adhere to the principles indicated in Table 1, and continue multiple antibiotics beyond the time that they are potentially useful. Unfortunately, it only takes a few days before the patient is then colonized with far more resistant and often more virulent organisms.

The second reason for administering combinations of antibiotics is to achieve synergy - more effective killing of the organism with both agents working synergistically than can be achieved by single antibiotics. This has been proven effective for a limited number of organisms, such as enterococcus and gram-negative enteric bacteria, especially in patients with compromised host defenses. Consultation with an infectious disease specialist is often important to identify those few situations where synergy may be useful, because some antibiotic combinations may actually be antagonistic and may interfere with effective therapy.

Table

TABLE 5Principles for the Use of Prophylactic Antibiotics

TABLE 5

Principles for the Use of Prophylactic Antibiotics

The third reason for giving combinations of antibiotics is to reduce the emergence of resistance. This is especially important in the treatment of tuberculosis. Finally, combinations of the antibiotics may be useful in certain cases where synergy permits the use of lower concentrations of a particular toxic antibiotic (eg, amphotericin and 5-flucytosine in fungal meningitis).

For the most part, antibiotic combinations will be given as presumptive therapy in high-risk patients and should be modified as soon as the proper cultures, taken prior to the initiation of therapy, identify the true causative agent.

ANTIBIOTIC PROPHYLAXIS

The concept of antibiotic prophylaxis has been widely studied. Physicians often talk of "covering their patients" with antibiotics in an effort to prevent them from getting a serious infection. Such a practice is often counterproductive. In fact, it takes only a few days for the body to become colonized with organisms resistant to the antibiotics being used. We invite a resistant superinfection by "covering" a persistantly high-risk individual for an indefinite time with broad-spectrum antibiotics.1'18

The principles shown in Table 5 identify circumstances where prophylactic therapy may be of use.10 In general, we recommend prophylactic antibiotics only in situations where the antibiotic coverage will be for a short period of exposure (eg, surgical prophylaxis for 1 day or less for patients with the potential of wound contamination at the time of surgery). Other examples include post-exposure prophylaxis for patients exposed to pertussis, meningococcemia, or Haemophilus influenzae type B.

The other situation where prophylaxis may be useful is in the prevention of infections with organisms that continue to be susceptible to the antibiotic being used (eg, penicillin in the prevention of Streptococcus pyogenes infections in patients with rheumatic fever).

The final reason for using antimicrobial prophylaxis is in the prevention of urinary tract infection where the drug given may be concentrated in the urine and so well absorbed that it gives low levels anywhere else, thus delaying the emergence of resistant strains. Although this may work for some period of time, there are now increasing reports of recurrent urinary tract infections with resistant organisms in patients being treated with long-term prophylaxis - suggesting that other preventive measures may deserve greater emphasis.19'20

CONCLUSIONS

Antibiotics are one of the most important drug discoveries of the 20th century. They have proven especially useful in children, who tend to be more susceptible to bacterial infections at a young age. Although many parents (and health care providers) would like to embrace the proposal that there must be an effective prescription therapy for every disease, that is overly optimistic because we recognize that there are significant costs and risks to overprescription. The guidelines in this article provide evidence-based principles for effective antimicrobial therapy, with the emphasis on treating only those patients who have illnesses likely to respond. The admonition "prove it or don't use it" emphasizes the importance of diagnostic testing in patients being treated with parentela! antibiotics. This is necessary to tell us when to modify antibiotic treatment and when to stop. This approach does not restrict current options, but rather preserves therapeutic alternatives for the future.

REFERENCES

1. Swartz MN. Use of antimicrobial agents and drug resistance. N Engl J Med. 1997;337:491-492.

2. De Santis G, Harvey KJ, Howard D, Mashford ML, Moulds RF. Improving the quality of antibiotic prescription patterns in general practice: the role of educational intervention. Med J Ausi. 1994;160:502-505.

3. Neu H. The crisis in antibiotic resistance. Science. 1992;257:1064-1073.

4. Klein JO. Protecting the therapeutic advantage of antimicrobial agents used for otitis media. Pediatr Infect Dis J. 1998;17:571-575, 580.

5. Evans RS, Pestotnik SL, Classen DC, et al. A computerassisted management program for antibiotics and other antiinfective agents. N Engl J Med. 1998^38:232-238.

6. Pestotnik SL, Classen DC, Evans RS, Burke JP. Implementing antibiotic practice guidelines through computer-assisted decision support: clinical and financial outcomes. AMM intern Mea. 1996;124:884-890.

7. Doern GV, Vautour R, Gaudet M, Levy B. Clinical impact of rapid in vitro susceptibility testing and bacterial identification. / Gin Microbio/. 1994;32:1757-1762.

8. Levy SB. Multidrug resistance: a sign of the times. N Engl } Med. 1998;338:1376-1378.

9. Fonseca SN, Ehrenkranz RA, Baltimore RS. Epidemiology of antibiotic use in a neonatal intensive care unit. Infect Control Hasp Epidemial. 1994;15: 156-1 62.

10. American Academy of Pediatrics. Antimicrobial prophylaxis. In: Peters GE, ed. Red Book: Report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL: American Academy of Pediatrics; 1997:593-603.

11. Dellinger EP, Gross PA, Barrett TL, et al. Quality standard for antimicrobial prophylaxis in surgical procedures: the Infectious Diseases Society of America. Infect Control Hasp Epidemial. 1994;1 5:1 82-1 88.

12. Squire EN Jr, Reich HM, Merenstein GB, Favara BE, Todd JK. Criteria for the discontinuation of antibiotic therapy during presumptive treatment of suspected neonatal infection. Pediatr Infect Dis J. 1982;1:85-90.

13. Schentag JJ, Ballow CH, Fritz AL, et al. Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory. Diagn Microbio! Infect Dis. 1993;! 6:255-264.

14. Todd JK. Office laboratory diagnosis of skin and soft tissue infections. Pediatr Infect Dis J. 1985;4:84-87.

15. Traylor KK, Todd JK. Needle aspirate culture method in soft tissue infections: injection of saline vs. direct aspiration. Pediatr Infect Dis ]. 1998;17:840-841.

16. Todd JK. Antimicrobial therapy of pediatrie infections. Current Pediatrie Diagnosis and Treatment, 12th ed. Norwalk, CT: Lange Medical Book; 1995:1112-1119.

17. Briceland LL, Nightingale CH, Quintiliani R, Cooper BW, Smith KS. Antibiotic streamlining from combination therapy to monotherapy utilizing an interdisciplinary approach. Arch Intern Med. 1988;I48:2019-2022.

18. King JW, White MC, Todd JR, Conrad SA. Alterations in the microbial flora and in the incidence of bacteremia at a university hospital after adoption of anukacin as the sole formulary aminoglycoside. CUn Inject Dis. 1992;14.-908-915.

19. Todd JK. Prevention of urinary tract infection in children. In: Review Newsletter. New York: Churchill Uvingstone; 1997:29-32.

20. Todd JK Management of urinary tract infections: children are different. Pediatr Rev. 1995;16: 190-1%.

TABLE 1

Principles for Starting, Modifying, and Stopping Antibiotic Therapy for Hospital lnpatients

TABLE 2

Steps In Decision Making for the Use of Pa renteral Antimicrobial Agents

TABLE 3

Steps In Switching From Parenteral to Oral Therapy for an Initially Serious Infection

TABLE 4

Principles for the Use of Antibiotic Combinations

TABLE 5

Principles for the Use of Prophylactic Antibiotics

10.3928/0090-4481-19990701-09

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