Pediatric Annals

Antibiotic Update: Overview

Charles G Prober, MD

Abstract

This issue of Pediatric Annals is dedicated to the prudent and cost-conscious use of antibiotics in children. This topic is especially relevant in the current era because health care is so heavily focused on cost containment. Infections are one of the most common reasons for office visits and hospitalization of children. Further, about one-third of all prescribed drugs are antibiotics.1 Unfortunately, there are ample data demonstrating that antibiotics are prescribed incorrectly. The most common errors in prescribing include lack of indication, poorly selected agent, and incorrect dose.2 Rates of inappropriate antibiotic use in hospitalized patients range from 30% to 65%, and up to half of antibiotic prescriptions given to ambulatory patients apparently are not indicated. For example, many are prescribed for presumed viral upper respiratory tract infections.3,4 The results of overzealous use are being felt worldwide as antimicrobial resistance rises.5 Students of antimicrobials declare that "the pattern of discovery, exuberant use, and predictable obsolescence has been repeated after the introduction of each new antimicrobial agent."5 These observations regularly appear in sensational articles in the lay press that declare "the end of miracle drugs" (Newsweek. March 28, 1994:Cover). There can be no question that the appropriate use of antibiotics is the responsibility of every practitioner; "inappropriate or excessive use will affect the entire ecologic system and cannot be condoned."5

Although "the most important decision in the use of antibiotics is whether they should be used at all,"6 once they are prescribed we have an obligation to select the most effective, best tolerated, and ideally, least expensive therapeutic alternative. Fortunately, except for infections caused by multiply resistant pathogens, there usually are several therapeutic options from which to choose. The article by Drs Jacobs and Stimson outlines therapeutic options for serious bacterial infections in hospitalized children. They emphasize that host age and site of infection are the most important determinants. Additional factors include local patterns of drug resistance; host factors such as renal function, hepatic function, and drug allergies; and which antibiotics are available on the hospital formulary. The antimicrobial regimen can be adjusted according to the antimicrobial sensitivity of the isolated organism.

The prudent and cost-conscious therapy of suspected bacterial infections in hospitalized children includes many considerations beyond the selection of appropriate antibiotics. Examples are appropriate use of blood tests, radiologic evaluations, and bacteriologie studies. Common decisions include the "ideal" frequency of monitoring the complete blood cell count (CBC), acute-phase reactants such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), indices of renal function and hepatic function, and drug concentrations. The indications for bacteriologic follow-up and the need for costly radiologic imaging procedures also must be considered.

Although "critical pathways" attempt to outline an optimal intervention strategy, pathways have not been developed for the management of all serious infections. Furthermore, the need for individualization of patient care always will be evident. Before ordering any test, it is reasonable to ask whether the results of a specific follow-up evaluation likely will influence a therapeutic change. In the absence of clinical deterioration, it is unlikely that the frequent performance of CBC, ESR, or CRP will influence therapy. Although monitoring renal and hepatic function may be necessary for patients with progressive organ failure or in those receiving nephrotoxic or hepatotoxic drugs, repeated measures are unlikely to be of value in the absence of these factors. The only antibiotics for which monitoring of serum concentrations may be indicated are the aminoglycosides, vancomycin, and chloramphenicol. However, chloramphenicol is rarely the drug of choice for the treatment of infections in the United States, and there is controversy regarding the optimal method of monitoring serum concentrations of aminoglycosides…

This issue of Pediatric Annals is dedicated to the prudent and cost-conscious use of antibiotics in children. This topic is especially relevant in the current era because health care is so heavily focused on cost containment. Infections are one of the most common reasons for office visits and hospitalization of children. Further, about one-third of all prescribed drugs are antibiotics.1 Unfortunately, there are ample data demonstrating that antibiotics are prescribed incorrectly. The most common errors in prescribing include lack of indication, poorly selected agent, and incorrect dose.2 Rates of inappropriate antibiotic use in hospitalized patients range from 30% to 65%, and up to half of antibiotic prescriptions given to ambulatory patients apparently are not indicated. For example, many are prescribed for presumed viral upper respiratory tract infections.3,4 The results of overzealous use are being felt worldwide as antimicrobial resistance rises.5 Students of antimicrobials declare that "the pattern of discovery, exuberant use, and predictable obsolescence has been repeated after the introduction of each new antimicrobial agent."5 These observations regularly appear in sensational articles in the lay press that declare "the end of miracle drugs" (Newsweek. March 28, 1994:Cover). There can be no question that the appropriate use of antibiotics is the responsibility of every practitioner; "inappropriate or excessive use will affect the entire ecologic system and cannot be condoned."5

Although "the most important decision in the use of antibiotics is whether they should be used at all,"6 once they are prescribed we have an obligation to select the most effective, best tolerated, and ideally, least expensive therapeutic alternative. Fortunately, except for infections caused by multiply resistant pathogens, there usually are several therapeutic options from which to choose. The article by Drs Jacobs and Stimson outlines therapeutic options for serious bacterial infections in hospitalized children. They emphasize that host age and site of infection are the most important determinants. Additional factors include local patterns of drug resistance; host factors such as renal function, hepatic function, and drug allergies; and which antibiotics are available on the hospital formulary. The antimicrobial regimen can be adjusted according to the antimicrobial sensitivity of the isolated organism.

The prudent and cost-conscious therapy of suspected bacterial infections in hospitalized children includes many considerations beyond the selection of appropriate antibiotics. Examples are appropriate use of blood tests, radiologic evaluations, and bacteriologie studies. Common decisions include the "ideal" frequency of monitoring the complete blood cell count (CBC), acute-phase reactants such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), indices of renal function and hepatic function, and drug concentrations. The indications for bacteriologic follow-up and the need for costly radiologic imaging procedures also must be considered.

Although "critical pathways" attempt to outline an optimal intervention strategy, pathways have not been developed for the management of all serious infections. Furthermore, the need for individualization of patient care always will be evident. Before ordering any test, it is reasonable to ask whether the results of a specific follow-up evaluation likely will influence a therapeutic change. In the absence of clinical deterioration, it is unlikely that the frequent performance of CBC, ESR, or CRP will influence therapy. Although monitoring renal and hepatic function may be necessary for patients with progressive organ failure or in those receiving nephrotoxic or hepatotoxic drugs, repeated measures are unlikely to be of value in the absence of these factors. The only antibiotics for which monitoring of serum concentrations may be indicated are the aminoglycosides, vancomycin, and chloramphenicol. However, chloramphenicol is rarely the drug of choice for the treatment of infections in the United States, and there is controversy regarding the optimal method of monitoring serum concentrations of aminoglycosides and vancomycin. Indeed, the clinical value of monitoring serum vancomycin concentrations recently has been questioned,7,8 except perhaps among those with rapidly changing renal function, those receiving hemodialysis, and those who are not clinically responding to therapy.8

The prudent use of the bacterial culture improves the management of serious bacterial infections. Positive cultures confirm the diagnosis and facilitate the selection of the most appropriate antibiotics. Although there are no strict guidelines regarding the need and timing of follow-up cultures, there are some general criteria. If initial cultures were negative, such as in children with suspected bacterial pneumonia, and there are no changes in clinical status, there is little value in repeating cultures after antibiotics have been initiated. If initial cultures were positive and repeated cultures are easily obtained, such as cultures of blood or urine, follow-up cultures represent the best means for determining the adequacy of therapy. On the other hand, if follow-up cultures require the performance of an invasive procedure, such as a lumbar puncture, joint aspiration, or bone biopsy, they probably are not warranted unless the anticipated clinical response is not happening or there is clinical deterioration.

Imaging studies may be of value in the diagnosis and management of serious bacterial infections bur their liberal use can quickly drive up costs. Plain radiographs may be useful in the initial diagnosis of osteomyelitis, septic arthritis, and pneumonia. Radionucleotide scans are more sensitive in bone and joint infections and also may have a role in children with suspected pyelonephritis. Ultrasound has proven to be a valuable imaging procedure for infants and children with urinary tract infections. Computed tomography (CT) may be useful in the evaluation of children with central nervous system infections, such as those with suspected abscesses or complicated bacterial meningitis. In contrast, common examples of the overuse of imaging procedures include the performance of CT scans on all children with bacterial meningitis, follow-up bone scans in children with uncomplicated osteomyelitis, and frequently repeated chest radiographs in children with suspected bacterial pneumonia who are clinically stable or improving.

Drs Jacobs and Stimson also discuss hospital programs that can contribute to optimal antibiotic utilization with possible cost savings. These programs involve the collaborative efforts of the pharmacy, infectious diseases, and microbiology departments and include formulary review, therapeutic drug monitoring, antimicrobial guideline development, and the reporting of adverse drug reactions.

Optimal duration of antibiotic therapy for most bacterial infections has never been defined by randomized controlled trials. Rather, length of treatment has been guided by tradition. Patients should be treated until their infection has been bacteriologically eradicated and they are clinically improved, but beyond those endpoints, the decision to discontinue therapy is empiric. Savings can result from shortening the hospitalization and parenteral therapy. Dr Gutierrez provides an overview relevant to the transition from parenteral antibiotics administered in the hospital to oral antibiotics administered at home, a practice referred to as sequential or switch therapy. Dr Gutierrez carefully outlines requirements for a successful transition of therapy and optimal methods for monitoring effectiveness. Studies supporting the safety and efficacy of this transition of therapy date back nearly 30 years.9 The use of sequential parenteral and oral therapy in the management of bone and joint infections has been most studied, but there are other opportunities for this management strategy.10 Dr Gutierrez also discusses the potential role of home infusion therapy. This achieves uninterrapted parenteral administration of a drug while still realizing some advantages of early hospital discharge.

Dr Mason focuses on the management of common infections in ambulatory children. We do not lack therapeutic alternatives for common infections. In fact, oftentimes the most difficult decision facing clinicians is which of the myriad of available antibiotics is most appropriate. A review of Dr Mason's recommendations indicates that antibiotics that have "withstood the test of time" generally are preferred over newer agents. The older agents tend to be substantially less expensive and remain clinically effective. However, as a result of increasing antimicrobial resistance among bacteria responsible for mild to moderate infections, therapeutic recommendations are under a state of evolution. For example, although in most areas of the country amoxicillin remains the drug of first choice for the treatment of acute otitis media, increasing frequency of resistance among strains of Streptococcus pneumoniae, nontypable Hemophilus influenzae, and Moraxella catarrhalis jeopardizes the continued efficacy of this agent.11 Some of the newer agents are being marketed on the basis of their enhanced activity against these resistant bacteria. In addition, it often is claimed that the newer agents offer advantages in frequency of adverse events and improved convenience. In my opinion, the data supporting a meaningful reduction in side effects are not convincing, and many of the older drugs are known to be effective when administered at prolonged intervals. For example, more than 40 years ago, it was demonstrated that penicillin was equally effective in the treatment of pharyngitis caused by group A streptococcus, whether administered four times daily or twice daily.13

Optimal duration of therapy is as ill defined for mild to moderate outpatient infections as it is for serious inpatient infections. Increasing rates of antimicrobial resistance and rising health-care costs have helped stimulate recent recommendations to reduce the length of treatment of common infections. For example, it recently was suggested that reducing the length of therapy for uncomplicated otitis media from 10 to 5 days would be prudent in the United States.11 Considering the frequency of this infection, a reduction of 5 days would have an enormous impact on antibiotic utilization.

An important consideration in the acceptability of oral antibiotics is their palatability. As trite as this may seem, the best antibiotic will not be of value if a child is unwilling to swallow iti Janice Tarn, PharmD, summarizes recent literature on generic antibiotics, with special emphasis on their availability and taste.14,15 Dr Tarn also provides insight into the fiscal advantages of a generic therapeutic substitution policy and other stategies for antibiotic cost reduction within the managed care environment.16

The best management strategy for the young febrile child without an obvious source of infection is controversial. The empiric use of oral or parenteral antibiotics, while awaiting the results of cultures, has become a common strategy. Considering the frequency of febrile illnesses in children, management strategies involving empiric therapy will result in substantial antibiotic use. Dr Sectish reviews the strategic options available for the management of febrile infants, emphasizing that individualization of therapy should be based on an appreciation of the literature and the clinical status of the child. Dr Sectish also introduces the important considerations of parent preferences and physician treatment thresholds as relevant to the evaluation and management of febrile infants. Although a thoughtful "practice guideline" regarding the management of febrile infants has been published,17 it should be regarded as a starting point in the decision-making process, not as the only acceptable approach for all febrile children.

I believe that the authors of the articles in this issue of Pediatrie Annals have provided meaningful contributions toward the prudent and cost-conscious management of bacterial infections in children. Their recommendations represent a thoughtful analysis of the literature but they should not be regarded as the only approach. Specific antibiotic utilization practices should consider local bacterial resistance patterns, drug acquisition costs, and personal preferences. Due caution should be exercised in the uncritical adoption of the "latest and greatest" antibiotics; they tend to be substantially more expensive than their older counterparts, oftentimes without enhanced efficacy.

REFERENCES

1. Kennedy DL, Forber MB. Drug therapy for ambulatory pediatric patients in 1979. Pediatrics. 1982;70:26-29.

2. Soumerai SB, Ross-Degnan D. Drug prescribing In pediatrics: challenges for quality improvement. Pediatrics. 1990;86:782-784.

3. Prober CG, Gold R. Antibiotic abuse: spare the child. Canadian Medical Association Journal 1980;122:7-8.

4. Faryna A, Wergowske GL, Goldenberg K. Impact of therapeutic guidelines on antibiotic use by residents in primary care clinics. J Gen Intern Med. 1987;2: 102107.

5. Kunln CM. Resistance to antimicrobial drugs - a worldwide calamity. Ann Intern Med. 1993;118:557-561.

6. Melmon JCL, Morelli HF, eds. Clinical Pharmacology; Bask Principies in Therapeutics. New York, NY: Macmillan; 1971.

7. Cantu TG. Yamanaka-Yuen NA, Lietman PS. Serum vancomycin concentrations: reappraisal of their clinical value. CIm infect Dit. 1994;18:533-543.

8. Shafran SD. The serum vancomycin assay: a test of historic Interest. Canadian Journal of Infectious Diseases. 1995;6:67-68.

9. Green JH. Cloxacillin in treatment of acute osteomyelitis. BMJ. 1967;2:414-416.

10. Mandeif LA. Bergeron MG, Gribóle MJ, et ai. Sequential antibiotic therapy: effective cost management and patient care. Canadian Journal of Infectious Diseases. 1995,6:306-315.

11. Paradise JL. Managing otitis media: a time for change. Pediatrici. 1995;96:712-715.

12. Harrison CJ. Perspectives on newer oral antimicrobials: what do they add? Pediatr Infect Dis J. 1995;14:436-444.

13. Huang NN. High RH. Effectiveness of penicillin administeted orally at intervals of 12 hours. J Pediarr. 1953;42:532-536.

14. Samulak KM, El-Chaar GM, Rubin LG. Randomized, double-blind comparison of brand and generic antibiotic suspensions, 1: a study of taste in adults. Pediatr infect Dis J. 1996;15:14-17.

15. El-Chaar GM. Mardy G, Wehlou K, Rubin LG. Randomized, double-blind comparison of brand and generic antibiotic suspensions, II: a study of taste and compliance in children. Pediatr Infect Dis J. 1996;15:18-22.

16. American College of Surgeons. Therapeutic substitution and formulary systems. Ann Intern Med. 1990;113:160-163.

17. Baraff LJ, Bass JW1 Fleisher GR, et al. Practice guidelines for the management of infants and children 0 to 36 months of age with fever without source. Pediatrics. 1993;92:1-12.

10.3928/0090-4481-19961101-04

Sign up to receive

Journal E-contents