Pediatric Annals

The Management of Common Infections in Ambulatory Children

Wilbert H Mason, MD, MPH

Abstract

Bacterial gastroenteritis usually can be distinguished from viral infections epidemiologic and clinical observations. Bacterial disease is more likely to have high fever (39°C), severe abdominal pain, hematochezia, and tenesmus. The decision to perform stool cultures can be aided by an evaluation of the stool for leukocytes using methylene blue stain.49

The most common bacterial enteric pathogens in children include Salmonella and Shigella species, Cambylobacter jejuni, and enterotoxigenic and enterohemorrhagic strains of E coli.48 Antimicrobial therapy recommendations are summarized in Table 10.50 The treatment of enterohemorrhagic E coli infection is controversial because of data suggest treatment may precipitate hemolytic uremic syndrome.

Urinary Tract Infections

Urinary tract infections in children are common, with a cumulative risk in the first 10 years of life of 1 % for boys and 3% for girls. A third or more of these children will have recurrences.51 The diagnosis is problematic because symptoms are nonspecific and adequate specimen collection is difficult.51

A carefully obtained urine culture remains the gold standard for diagnosis.52 Midstream, clean-catch specimens obtained from older, cooperative patients may be adequate, especially if repeat cultures yield the same organism. For younger children and infants, suprapubic or catheter specimens are necessary. A recent study suggests catheter specimens are preferred.53 Bacterial counts of >105 colonies/mL from midstream clean-catch specimens suggest significant infection, while almost any growth from suprapubic specimens suggest a urinary tract infection.

Although many organisms, especially enteric pathogens, may cause urinary tract infection in children with normal urinary tract anatomy, 80% to 90% of infections are due to E colt. Recommended drugs for initial treatment include amoxicillin, amoxicillin clavulanate, an oral cephalosporin, trimethaprim-sulfamethaxazole, nitrofurantoin, or naldixic acid.51 Although short-course therapy regimens are popular in adults, 10 days of therapy are recommended for children.12'51 Repeat urine culture at 48 to 72 hours of treatment should be done to assure sterility. Adequate hydration, treatment of constipation, and removal of irritants, such as bubble bath, are also important.

Diagnostic imaging to identify evidence of renal parenchymal involvement or obstructive lesions have been discussed in the May 1996 issue of Pediatric Annah and elsewhere.51,52

SUMMARY

Antimicrobial therapy of infection in ambulatory children remains the cornerstone of the pediatrician's practice. Despite a cornucopia of newer antimicrobial agents, the older "tried and true" drugs continue to be favored based on their history of effectiveness, lack of toxicity, and low price.

It also is clear that the widespread use of antimicrobial agents has contributed to the development of resistance. We must reevaluate our antimicrobial use so that we only treat infections likely to benefit from antimicrobials. Better diagnostic techniques should be developed for rapid and accurate identification of pathogens. Finally, alternative therapeutic strategies should be investigated, such as shorter courses of treatment54 or use of vaccines,55 to lessen the selective pressure on the microbial flora. To fail to meet this challenge will mean the more rapid transition into the "postantibiotic era."56

1. Scheppert SM. Office vinta tot otitis media: United States, 1975-90. Advance Data From Vital and Health Statistics No. 2/4. Hyattsville. Md: National Center for Health Statistics; 1992.

2. Centers for Disease Control and Prevention. Addressing the emerging infectious disease threats. A prevention strategy for the United States: executive summary. MMWR Morb Mortal Wkly Rep. 1994;43(RR-5):1-18.

3. McCaig LF, Hughs JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. MMA 1995;273:214-219.

4. Neu HC. The crisis in antibiotic resistance. Science. 1992;257:1064-1073.

5. Doern GV. Resistance among problem pathogens in pediatrics. Pediatr Infect Dis J. 1995;14:420-423.

6. Harrison CJ. Perspective on newer oral antimicrobials: What do they add! Pediatr Infect Dis J. 1995;14:436-444.

7. Soyka LF, Robinson DS,…

Management of acute infections in children is the most frequent task of the office- or clinicbased pediatrician, after well-child care. Respiratory tract infections especially occupy a good deal of the pediatricians time. Indeed, otitis media is the second leading cause of office visits and the leading cause of emergency room visits.1 Treatment of respiratory tract infections frequently involves the use of antimicrobial agents. Antimicrobials are the second most commonly prescribed group of drugs, and most antimicrobials are prescribed for infections in ambulatory settings.2 In 1992, the number of treatment courses in the United States was 1.1 million, a 28% increase from 1980.3

The diagnoses for which oral antimicrobials were prescribed most frequently in 1992 were otitis media, upper respiratory tract infection, bronchitis, pharyngitis, and sinusitis, all common conditions in pediatrics. As a result, the rate of antimicrobial use in children (<15 years old) was over three times that of any other age group.3 The overall rate of antimicrobial use did not change significantly between 1980 and 1992, but increasing trends in the use of amoxicillin and broader spectrum cephalosporins were found.3

Widespread antimicrobial use has exerted selective pressure on bacterial pathogens with the result that we are now seeing the emergence of resistance among organisms once exquisitely susceptible to "first-line" antibiotics such as penicillins and macrolides.4,5 Although a profusion of oral antimicrobial agents introduced over the last several years, their appropriate role in treatment of pediatric ambulatory infections remains to be defined.6

This article reviews current practices of antimicrobial utilization and recent trends in the development of bacterial resistance. The types of oral agents and recommendations regarding therapy of specific infections will be presented.

COMMON PRACTICES IN THE USE OF ORAL ANTIMICROBIAL AGENTS IN PEDIATRICS

Antibiotics consume a substantial proportion of health-care dollars. For example, in 1 990, an estimated 20.6 million antibiotic prescriptions were written for the treatment of otitis media; one third of the prescriptions were for amoxicillin.2 If we assume the cost of 10 days of amoxicillin for a 10-kg child to be $4.60 (based on average wholesale cost to pharmacist for a brand-name preparation) and apply that figure to the prescriptions written for amoxicillin, the cost would be $31.6 million for that drug alone.

Inappropriate use of antibiotics adds substantially to these costs. In 1992, upper respiratory tract infection (based on ICD-9-CM Codes 460 and 465) was the second-most frequent respiratory diagnosis for antimicrobial drugs prescribed in the United States (17,922,000 episodes.)3 Numerous studies have shown that antimicrobial therapy of upper respiratory tract infections in children fails to shorten the course, minimize symptoms, or decrease complications of these infections.7'10 Obviously, treating only infections that would benefit from antibiotics would lessen the economic impact of oral antimicrobial use.

Unfortunately, several factors make specific and accurate diagnosis and treatment of common infections in children difficult. First, diagnostic criteria are vague. A diagnosis of acute otitis media, for example, is made by some practitioners when they find myringitis and by others only when there is redness, dullness, and purulent material behind the tympanic membrane. Second, even when a clinical diagnosis is sound, therapy is undertaken on an empiric basis because diagnostic tests to identify a pathogen are lacking. Microbiologic confirmation of the infecting pathogen rarely is available for otitis and sinusitis.11 Urinary tract infections in children frequently and inappropriately are diagnosed and treated on the basis of clinical symptoms alone because of the difficulties associated with obtaining an appropriate urine sample for culture.'2 Further, the difficulty in distinguishing diseases that respond to antibiotics from those of viral etiology leads to overtreatment in a variety of conditions: pneumonia is a common example. Finally, and at times most powerfully, the pressure to use antimicrobial agents in an outpatient setting comes from nonmedical considerations including patient (or parent) expectations, precedents (having prescribed the drug previously), and the desire on the part of the physician not to alienate the patient.13

DEVELOPMENT OF DRUG RESISTANCE

The widespread and often inappropriate use of oral antimicrobial agents has contributed to the development of resistance among previously susceptible pathogens.4,5,14,16 In the early 1970s, Hemophilus influenzae was uniformly susceptible to ampicillin. However, over the last two decades, the acquisition of plasmid-mediated beta- lactamase activity has resulted in resistance to ampicillin and amoxicillin for 20% of H influenza organisms in the United States.4,17 Over the same period of time, the rate of resistance to ampicillin and other antibiotics of Moraxella catarrhalis, a common pathogen in otitis media and bacterial bronchitis, has increased from nil to 75%.4

Table

TABLE 1Resistant Pneumococci: Break Points*

TABLE 1

Resistant Pneumococci: Break Points*

Of greatest concern is the recent emergence of antibiotic-resistant Streptococcus pneumoniae in the United States.18,19 Penicillin resistance was uncommon prior to 1987,20 but recent reports suggest rapid emergence of both relative and high-level penicillin-resistant pneumococci (PRP) (Table 1).18,20,21 Three recent reports document increasing rates of PRP: over a 15year period, resistance went from 5% in the 1979-1987 period,20 to 6.7% in 1991-1992,18 and 23.6% in 1994.21 Rates of resistance have been higher in organisms isolated from children compared with adults, and several studies have implicated prior beta-lactam antimicrobial use and day-care attendance as risk factors for infection with PRP.22-24

Also alarming is that PRP organisms frequently are resistant to other antimicrobial agents including cephalosporins, macrolides, and sulfa drugs.18,20,21 There are now significant rates of resistance to cefuroxime (2.8% to 12%),18,21 erythromycin (0.3% to 1.3% to 10%), and sulfamethoxazole/trimethoprim (0.6% to 10.7% to 18%).18,20,21

Increased morbidity and mortality have resulted from infections caused by multiply resistant bacteria and the annual unrecognized social costs attributable to antibiotic resistance among all resistant strains in the United States is estimated to be between $75 million and $7.5 billion annually.25 Clearly, our approach to the management of childhood infections in the ambulatory setting requires modification if we are to control the rate of antimicrobial resistance and practice efficient, cost-conscious medicine.

Table

TABLE 2Oral Antimicrobial Activity Against Specific Bacteria*

TABLE 2

Oral Antimicrobial Activity Against Specific Bacteria*

Table

TABLE 3Pharmacokinetics of Oral Antibiotics

TABLE 3

Pharmacokinetics of Oral Antibiotics

ORAX ANTIMICROBIAL AGENTS IN PEDIATRICS

A profusion of new oral antimicrobial agents has been introduced over the last several years. New agents have been developed to address antimicrobial resistance, and some are marketed for improved pharmacokinetics and safety to enhance convenience of dosing, tolerance, and compliance. While convenience and antimicrobial activity against certain pathogens has been improved, it is not clear whether the newer drugs are superior to more tried and true agents, especially when costs are considered.

A brief overview of the agents presendy available for oral treatment of children follows. Tables 2 and 3 summarize the antibacterial activities and pharmacokinetic profiles of the drugs. Table 4 summarizes gastrointestinal side effects - the most common adverse effect.

Penicillins

Penicillins continue to be one of the most widely prescribed classes of antibiotics in pediatrics.2 Amoxicillin has largely replaced ampicillin in this class because of its superior pharmacokinetic characteristics and decreased tendency to cause diarrhea. Activity of amoxicillin and ampicillin are similar except amoxicillin is not as active against Shigella as is ampicillin.26 Activity of amoxicillin against H influenzae, M catanhalis, Staphylococcus aureus, and the Enterobacter-iaceae have decreased over the years. Addition of clavulanate, a beta-lactamase inhibitor, to amoxicillin enhanced its stability in the presence of TEM beta-lactamase produced by H influenzae, M catanhalis, and Escherichia coli. This has extended its activity against these organisms anaerobes. Unfortunately, amoxicillin-clavulanate has a significantly increased incidence of diarrhea, possibly due to increased small bowel motility induced by clavulanate27 and change in bowel flora. Administration with food seems to decrease diarrhea.

Amoxicillin remains the drug of choice for initial treatment of otitis media and sinusitis in most areas of the United States. Amoxicillin-clavulanate is a reasonable alternative if beta-lactamase producing organisms are suspected. Amoxicillin-clavulanate also is preferred in the prophylaxis and treatment of animal bites because of its activity against S aureus as well as anaerobes including Pasturella multocida.

Cephalosporins

No class of antibacterial agents has been exploited more effectively by drug companies than the cephalosporins. Based on chronology of introduction and antibacterial activities, the agents in this class are divided into three generations. First-generation cephalosporins are active primarily against gram-positive cocci including S aureus. They are used as alternatives in patients allergic to the penicillin-related antibiotics, especially for treatment of cellulitis and pharyngitis.

Second-generation cephalosporins retain good activity against gram-positive cocci but have enhanced activity against gram-negative pathogens such as H influenzae and M catanhalis as well as some Enterobacteriacea like E coli, Klebsiella pneumoniae, and indol-negative Proteus species. Cefaclor was the first oral second-generation cephalosporin antibiotic and was introduced for treatment of otitis media. Its usefulness is compromised by a relatively high rate of serum sickness-like reactions28 and suboptimal activity against beta-lactamase producing respiratory pathogens.

Cefuroxime axetil has improved beta-lactamase stability compared with cefaclor and improved pharmacokinetic characteristics permitting twice daily dosing. It has performed well in clinical trials for otitis media, pharyngitis, plus lower respiratory and urinary tract infections also is effective for Lyme's disease. Unfortunately, taste is unacceptable to many children.

Cefprozil was introduced most recently and has similar pharmacokinetic characteristics and activity to cefuroxime. But cefprozil is somewhat less active against beta-lactamase producing strains. Its indications include infections of the respiratory tract and soft tissue. Serum sickness-like reactions to cefprozil have been reported, however.29

Table

TABLE 4Gastrointestinal Side Effects of Oral Antibiotics

TABLE 4

Gastrointestinal Side Effects of Oral Antibiotics

Loracarbef is identical to cefaclor in chemical structure except for the absence of a sulfur moiety on the dihydrothiazine ring. This change has conferred added beta-lactamase stability and seems to have diminished serum sickness reactions seen with cefaclor. It was rated best tasting of several oral suspensions in a recent trial.30

The third-generation cephalosporins have enhanced activity against gram-negative enteric and respiratory pathogens but are somewhat less active against staphylococcal and streptococcal pathogens than first- and second-generation agents. The oral suspensions of this group also have longer half-lives, which allow once-daily dosing many infections.

Cefixime has been available for the longest time and is effective in respiratory and urinary tract infections. It is quite palatable,30 but it has relatively poor activity against penicillin-susceptible strains of S pneumoniae and high rates of diarrhea.

Cefpodoxime proxetil has better activity against penicillin-susceptible strains of S pneumoniae and S aureus than Cefixime and retains excellent activity against H influenzae and M catanhalis. Indications for use are similar to Cefixime but palatability is inferior to other cephalosporins.

Ceftibuten is the most recently released agent in this class. Its activity against S pneumoniae and S aureus is poor but high sustained serum concentrations and penetration into middle ear fluid are observed.31 Its indications are similar to other agents in this class.

Macrolides

Erythromycin is useful in the treatment of skin, softtissue, and respiratory infections in patients allergic to beta-lactam antibiotics. In addition to streptococcal pharyngitis and otitis media (when combined with sulfisoxazole), pediatric indications for erythromycin preparations includes infections Mycoplasma pneumoniae, Ureaplasma urealyticum, Bordetella pertussis, Campylobacter, and Chlamydia. The major complication of erythromycin dierapy is vomiting and abdominal cramping due to irritation of gastric and intestinal mucosa. Interference with dieophylline metabolism also occurs.

Table

TABLE 5Baseline Treatment Costs of Selected Antimicrobials for a 10-Day Course in a 10-kg Child*

TABLE 5

Baseline Treatment Costs of Selected Antimicrobials for a 10-Day Course in a 10-kg Child*

Table

TABLE 6Most Common Bacterial Pathogens in Acute Otitis Media*

TABLE 6

Most Common Bacterial Pathogens in Acute Otitis Media*

Two newer agents, clarithromycin (a macrolide) and azithromycin (an azalide), recently were introduced for pediatric use.33 Their antimicrobial activities are similar to those of erythromycin except azithromycin is four to eight times more active against H influenzae.™ Their most notable characteristic is their nonlinear, tissue-directed pharmacokinetic properties. Tissue levels of clarithromycin and azithromycin are as much as 4 and 12 times higher, respectively, than erythromycin.34 Effective tissue levels may be maintained for 4 days after a dose of azithromycin. These features permit less frequent doses and shorter courses of therapy for certain infections. Clarithromycin, like erythromycin, elevates serum levels of theophylline. The effect of azithromycin on theophylline metabolism is apparently less than the macrolides but monitoring theophylline levels is still recommended.

MANAGEMENT OF SPECIHC INFECTIONS IN AMBULATORY CHILDREN

The outpatient management of infectious diseases in pediatrics has become complicated in the last several years. New organisms associated with certain clinical syndromes have been identified (eg, Chhmydia pneumoniae and Arcanobacterium hemolyticum cause pharyngitis) and older pathogens are becoming increasingly resistant to antibiotics. Physicians need to consider clinical and epidemiological factors carefully when deciding how to manage patients. The patient's environment and "antibiotic history" may influence the choice of antimicrobial agent. Day-care attendance or multiple courses of beta-lactam antibiotics in the past might argue for agents resistant to beta-lactamase inactivation. But, to reduce selective pressure of antibiotics on the development of bacterial resistance, physicians also must guard against the overzealous use of antimicrobials.

Antibiotic prescribing has become more challenging as the number of agents has proliferated and managed care has required that cost be considered in the management of infections in ambulatory patients. There are several factors to be considered in the selection of an antimicrobial agent:

Table

TABLE 7Antimicrobial Agents Available for Acute Otitis Media Therapy

TABLE 7

Antimicrobial Agents Available for Acute Otitis Media Therapy

* clinical and microbiological effectiveness,

* convenience,

* complications (eg, allergy, intolerance, and interactions),

* compliance, and

* cost.

First, the agent should have clinical and microbiologic activity against the bacteria proven or suspected to be causing infection. Practitioners must be knowledgeable about the susceptibilities of important pathogens in their practice or community. Second, convenience of dosing should be considered, especially when doses might be missed because of a unreliability of caregivers. Medications that allow dosing before and after work or school might be preferable. Third, possible complications related to drug allergies, intolerance, or the prescription of other medications that might interfere with action of the antibiotic. Fourth, compliance with the prescribed treatment is of obvious importance. Less frequent dosing regimens, shorter treatment courses, and palatable medications favor successful completion of therapy. Finally, an important factor influencing selection of an oral antibiotic is the wide variation in cost (Table 5). Many health maintenance organizations and government-funded plans have specified formularies, restricting prescriptions to a selected list of antibiotics.

Otitis Media

Pediatricians see more children for otitis media than any other illness,35 and this is the most common reason for prescribing antibiotics.16 MuCh of the antimicrobial resistance among H influenzae and S pneumoniae has been attributed to treatment of otitis.16 These observations have caused many knowledgeable practitioners and investigators to reevaluate the basic approach to the management of otitis media.35,36

Figure. Management of acute otitis media in areas of low and high penicillin-resistant pneumococci (PRP) prevalence. An estimated 3% of cases of acute otitis media fail to respond to amoxicillin based on assumptions of a 30% rate of acute otitis media due to pneumococci, a 10% prevalence of PRP, and a 10% to 20% rate of spontaneous resolution of acute otitis media due to pneumococci. (Adapted from reference 19).

Figure. Management of acute otitis media in areas of low and high penicillin-resistant pneumococci (PRP) prevalence. An estimated 3% of cases of acute otitis media fail to respond to amoxicillin based on assumptions of a 30% rate of acute otitis media due to pneumococci, a 10% prevalence of PRP, and a 10% to 20% rate of spontaneous resolution of acute otitis media due to pneumococci. (Adapted from reference 19).

As a crucial first step, more specific definitions of acute otitis media and otitis media with effusion or serous otitis media have been suggested.36 Acute otitis media is defined as middle ear effusion PLUS otalgia, marked tympanic redness, or distinct fullness or bulging of the tympanic membrane.36 Others suggest less stringent criteria such as presence of effusion and signs of acute illness that may include the above otologic findings and systemic signs of fever, irritability, or vomiting.35 Otitis media with effusion is middle ear effusion without signs of local or systemic infection.35,36

The etiologic agents of acute otitis media are listed in Table 6. Viruses have been isolated from about 20% of middle ear fluids in acute otitis media,37 and other pathogens such as M pneumoniae and Chlamydia trachomatis are uncommon causes. Any antibiotic selected to treat acute otitis media should be active against the three most common infections, S pneumoniae, H influenzae, and M catarrhalis. Currently, 13 oral agents and 1 parenteral drug are recognized as being effective (Table 7). These agents have acceptable microbiologic activity and pharmacokinetic characteristics.35,38

Identification of the "optimal" drug problematic for several reasons. Many clinical trials studied too few patients to reach valid conclusions regarding efficacy. Also, untreated acute otitis media will resolve spontaneously in a high percentage of patients without antimicrobial therapy.39 Treatment failures, on the other hand, are often due to factors other than microbiologic failure of the antibiotic.40,41

Amoxicillin remains the preferred drug for the initial therapy of otitis media in children.35,42 Its long history of safety, effectiveness, and relatively low cost suggests it should continue to be used. Klein35 has calculated the expected failure rate of amoxicillin considering current estimated rates of resistance of H influenzae, M catarrhalis, and S pneumococcus, and the expected rates of spontaneous resolution of acute otitis media caused by these agents. He concludes amoxicillin as primary therapy should lead to a failure rate of 10% to 15%. Higher rates of failure suggest a higher prevalence of beta-lactamase production alternative agents might be considered for primary therapy.

Acute otitis media that fails to resolve with amoxicillin should be treated based on susceptibility of important pathogens in the community and the selection criteria outlined earlier. An approach to management of acute otitis media with regard to PRP is outlined in the Figure.

Fluid persists in the middle ear for weeks to months following treatment of acute otitis media. Two weeks after starting therapy, 70% of children will have effusion. This will persist in 40% at 4 weeks and 20% at 8 weeks. The management of otitis media with effusion is controversial, but many authors feel the common practice of multiple or prolonged courses of antibiotics should be abandoned.36,42

Antibiotic prophylaxis for recurrent acute otitis media can be effective but is frequently used for excessive durations and in poorly selected patients. Criteria for prophylaxis include children with three episodes of acute otitis media in 6 months or four in 12 months. Children with a single infection in the first 6 months of life and a strong family history of acute otitis media or with two infections in the first year of life should be considered for prophylactic therapy. Sulfisoxazole 50 mg/kg/day or amoxicillin 20 mg/kg/day once daily throughout the respiratory viral season or given only during episodes of upper respiratory tract infection are recommended.36

Sinusitis

The management of sinusitis in children has been reviewed recently.43,44 Distinguishing sinusitis from an acute upper respiratory tract infection or chronic nasal allergy can be difficult. Symptoms and signs useful in differentiating these conditions are listed in Table 8. The diagnosis usually can be made clinically in children aged 2 to 6 years on the basis of persistent respiratory symptoms (>10 days) such as nasal discharge and cough or a "severe" upper respiratory tract infection with high fever (eg, (>39.5°C). Approximately 90% of such children have positive plain films of the sinuses and about 70% will have positive cultures of specimens obtained by antral aspiration. Hence, in this age group, roentgenograms are not necessary. In children older than 6 years, symptoms are not an accurate reflection of sinus disease, and sinus films should be obtained.45

Table

TABLE 8Differentiation of Acute Sinusitis From Upper Respiratory Tract Infections (URI) in Children*

TABLE 8

Differentiation of Acute Sinusitis From Upper Respiratory Tract Infections (URI) in Children*

The bacteriology of acute sinusitis in children is virtually identical to that of acute otitis media with S pneumoniae, H influenzae, and M catanhalis as the most common pathogens. Staphylococcus pyogenes and S aureus occasionally cause acute sinusitis. Staphylococcus aureus and anaerobes are responsible for most cases of chronic infections.43,44

The management of sinusitis is similar to that of acute otitis media in children; amoxicillin is the drug of choice in most cases. Spontaneous resolution occurs in 40% to 45% of cases, and infections due to beta-lactamase producing organisms often respond to amoxicillin. Alternative therapies are the same as for acute otitis media.43 Children who experience a rapid response to therapy require 10 days of treatment; those who respond more slowly should be treated for 7 days after they become symptom free.

Tonsillopharyngitis

Tonsillopharyngitis is a common upper respiratory tract infection in pediatric patients. Numerous viral, bacterial, and fungal agents have been associated with pharyngitis in pediatric patients, the majority of which cause self-limited infections without significant sequelae (Table 9). Identifying S pyogenes (group A beta-hemolytic streptococci) is important, considering the reappearance of invasive streptococcal infections46 and rheumatic fever.47

Clinical findings cannot reliably distinguish between pharyngitis caused by beta-hemolytic streptococci and other pathogens, although sudden onset, dysphagia, fever, headache, abdominal pain, palatal petechiae, and anterior cervical lymphadenitis favor the diagnosis of streptococcal disease.47 Specific microbiologic diagnosis should be sought on all patients suspected of having streptococcal pharyngitis. Antigen assays are specific but not sensitive in the identification of group A beta-hemolytic streptococci. The throat culture remains the gold standard.

Penicillin remains the drug of choice for treatment of streptococcal pharyngitis. Oral or intramuscular forms can be used; sustained serum antibiotic concentrations for 10 days is recommended.47 Erythromycin therapy is an acceptable alternative in penicillin-allergic patients. Azithromycin as a 5-day course has been approved as an alternative, but more experience is necessary before routine use can be recommended.

Table

TABLE 9Microblologic Findings in Children With Febrile Exudative Pharyngitis

TABLE 9

Microblologic Findings in Children With Febrile Exudative Pharyngitis

Microbiologic cure appears to occur more frequently following therapy with cephalosporins compared with penicillins.38 However, there is no evidence cephalosporins lessen rheumatologic complications. In view of its low price and long history of safety and effectiveness, most authorities still favor penicillin.38,47

Gastroenteritis

Acute gastroenteritis is a common pediatric condition most often due to viruses, especially rotavirus.48 Bacterial enteric infections in otherwise healthy children are usually self-limited. However, malnourished children or those with immunodeficiency syndromes, may have life threatening infections.

Table

TABLE 10Therapy of Infectious Enteric Illnesses

TABLE 10

Therapy of Infectious Enteric Illnesses

Bacterial gastroenteritis usually can be distinguished from viral infections epidemiologic and clinical observations. Bacterial disease is more likely to have high fever (39°C), severe abdominal pain, hematochezia, and tenesmus. The decision to perform stool cultures can be aided by an evaluation of the stool for leukocytes using methylene blue stain.49

The most common bacterial enteric pathogens in children include Salmonella and Shigella species, Cambylobacter jejuni, and enterotoxigenic and enterohemorrhagic strains of E coli.48 Antimicrobial therapy recommendations are summarized in Table 10.50 The treatment of enterohemorrhagic E coli infection is controversial because of data suggest treatment may precipitate hemolytic uremic syndrome.

Urinary Tract Infections

Urinary tract infections in children are common, with a cumulative risk in the first 10 years of life of 1 % for boys and 3% for girls. A third or more of these children will have recurrences.51 The diagnosis is problematic because symptoms are nonspecific and adequate specimen collection is difficult.51

A carefully obtained urine culture remains the gold standard for diagnosis.52 Midstream, clean-catch specimens obtained from older, cooperative patients may be adequate, especially if repeat cultures yield the same organism. For younger children and infants, suprapubic or catheter specimens are necessary. A recent study suggests catheter specimens are preferred.53 Bacterial counts of >105 colonies/mL from midstream clean-catch specimens suggest significant infection, while almost any growth from suprapubic specimens suggest a urinary tract infection.

Although many organisms, especially enteric pathogens, may cause urinary tract infection in children with normal urinary tract anatomy, 80% to 90% of infections are due to E colt. Recommended drugs for initial treatment include amoxicillin, amoxicillin clavulanate, an oral cephalosporin, trimethaprim-sulfamethaxazole, nitrofurantoin, or naldixic acid.51 Although short-course therapy regimens are popular in adults, 10 days of therapy are recommended for children.12'51 Repeat urine culture at 48 to 72 hours of treatment should be done to assure sterility. Adequate hydration, treatment of constipation, and removal of irritants, such as bubble bath, are also important.

Diagnostic imaging to identify evidence of renal parenchymal involvement or obstructive lesions have been discussed in the May 1996 issue of Pediatric Annah and elsewhere.51,52

SUMMARY

Antimicrobial therapy of infection in ambulatory children remains the cornerstone of the pediatrician's practice. Despite a cornucopia of newer antimicrobial agents, the older "tried and true" drugs continue to be favored based on their history of effectiveness, lack of toxicity, and low price.

It also is clear that the widespread use of antimicrobial agents has contributed to the development of resistance. We must reevaluate our antimicrobial use so that we only treat infections likely to benefit from antimicrobials. Better diagnostic techniques should be developed for rapid and accurate identification of pathogens. Finally, alternative therapeutic strategies should be investigated, such as shorter courses of treatment54 or use of vaccines,55 to lessen the selective pressure on the microbial flora. To fail to meet this challenge will mean the more rapid transition into the "postantibiotic era."56

REFERENCES

1. Scheppert SM. Office vinta tot otitis media: United States, 1975-90. Advance Data From Vital and Health Statistics No. 2/4. Hyattsville. Md: National Center for Health Statistics; 1992.

2. Centers for Disease Control and Prevention. Addressing the emerging infectious disease threats. A prevention strategy for the United States: executive summary. MMWR Morb Mortal Wkly Rep. 1994;43(RR-5):1-18.

3. McCaig LF, Hughs JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. MMA 1995;273:214-219.

4. Neu HC. The crisis in antibiotic resistance. Science. 1992;257:1064-1073.

5. Doern GV. Resistance among problem pathogens in pediatrics. Pediatr Infect Dis J. 1995;14:420-423.

6. Harrison CJ. Perspective on newer oral antimicrobials: What do they add! Pediatr Infect Dis J. 1995;14:436-444.

7. Soyka LF, Robinson DS, Lachant N, Monaco J. The misuse of antibiotics for treatment of upper respiratory tract infections in children. Pediatrics. 1975;55:552-556.

8. Todd JK, Todd N, Damato J, Todd WA. Bacteriology and treatment of purulent nasopharyngitis: a double blind, placebo-controlled evaluation. Pediatr Infect Dis. 1984;3:226-232.

9. Sutrisna B, Frerichs RR, Reingold AL. Randomized, conrrolled trial of effectiveness of ampicillin in mild acute respiratory infections in Indonesian children. Lancet. 1991;338:471-474.

10. Hcikkinen T, Ruskanen O, Zicgler T, Waris M, Puhakka H. Short term use of amoxicillin-clavulanate during upper respiratory tract infection for prevention of acute otitis media. J Pediatr. 1995;126:313-316.

11. Esposito AL. Role of oral antimicrobial drugs in the treatment of respiratory tract Infections: overview and summary of newer agents. Infectious Disease in Clinical Practice. 1995;4(suppl):S250-S258.

12. Shortliffe LMD. The management of urinary tract infections in children without urinary tract abnormalities. Pediatr Clin North Am. 1995;22:67-73.

13. Bradley CP. Uncomfortable prescribing decisions: a critical incident study. Br Med J. 1992;304:294-296.

14. Rockefeller University Workshop, Special report. Mulriplc-antibiotic-resistant pathogenic bacterial. N Engl ; Med. 1994;330:1247-1251.

15. Tenover FC, Hughes JM. The challenges of emerging infectious diseases: Development and spread of multiply-resistant bacterial pathogens. JAMA. 1996;275:300-304.

16. American Society for Microbiology. Report of the ASM Task Force on Antibiotic. Washington, DC: American Society for Microbiology; 1995.

17. Doren OV, Jorgensen JH, Thornsberty C et al. National collaborative study of the prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae. Antimicrobial resistance Chemother. 1988;32:180-185.

18. Breiman RF, Butlet JC. Tenover FC, et al. Emergence of drug-resistant pneumococcal infections in the United States. JAMA. 1994;271:1831-1835.

19. McCracken GH. Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics. PeoW Infect Dis J. 1995;14:424-428.

20. Spika JS, Facklam RR, Plikaylis BD, Oxtoby MJ. The Pneumococcal Surveillance Working Group. Antimicrobial resistance of Streptococcus pneumoniae in the United States, 1979-1987. J Infect Dis. 1991;163:1273-1278.

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TABLE 1

Resistant Pneumococci: Break Points*

TABLE 2

Oral Antimicrobial Activity Against Specific Bacteria*

TABLE 3

Pharmacokinetics of Oral Antibiotics

TABLE 4

Gastrointestinal Side Effects of Oral Antibiotics

TABLE 5

Baseline Treatment Costs of Selected Antimicrobials for a 10-Day Course in a 10-kg Child*

TABLE 6

Most Common Bacterial Pathogens in Acute Otitis Media*

TABLE 7

Antimicrobial Agents Available for Acute Otitis Media Therapy

TABLE 8

Differentiation of Acute Sinusitis From Upper Respiratory Tract Infections (URI) in Children*

TABLE 9

Microblologic Findings in Children With Febrile Exudative Pharyngitis

TABLE 10

Therapy of Infectious Enteric Illnesses

10.3928/0090-4481-19961101-08

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