Pediatric Annals

Presumptive Antibiotic Therapy for Hospitalized Children With Sepsis and Meningitis: Cost-Effective Analysis and Antibiotic Restriction Guidelines

Richard F Jacobs, MD; J Mel Stimson, PHARMD

Abstract

* intensive care unit patient,

* <3 months of age when therapy is expected to exceed 72 hours,

* renal insufficiency,

* concomitant use of other nephrotoxic drugs,

* central nervous system infections, and e altered body composition.

The goals of this program are to aid physicians in dosing antimicrobials with a narrow therapeutic margin and allow cost savings for the institution.

ANTIBIOTIC RESTRICTION GUIDELINES

Antibiotic restriction guidelines are an effective method of preserving an antibiotic for use in patients with resistant organisms and limiting the use of costly agents when less expensive alternatives are available and appropriate.19 Use of certain antibiotics can be restricted to specific services or limited to use in patients with specific diseases. For example, at our institution, gentamicin and tobramycin are available to any physician. However, to control costs and preserve the usefulness of amikacin for patients with organisms that are resistant to other aminoglycosides, amikacin can only be used if approved by the infectious disease service.

Antimicrobial utilization trends over time are also beneficial in formulary management decisions. The pharmacy and therapeutics committee of our institution reviews antimicrobial utilization patterns each quarter. Utilization patterns are separated by therapeutic class and include the number of prescriptions written, the number of doses dispensed, and institutional acquisition expenditures of each agent used in the therapeutic class. Sudden increases or changes in utilization can be identified. If necessary, more focused reviews can be undertaken to further analyze the trend and identify strategies to improve utilization guidelines. Physician feedback and education are critical elements of these reviews.

Amikacin Restriction Guidelines

A significant increase in the utilization of amikacin in 1993 was noted during the regular reviews presented to the pharmacy and thetapeutics committee (Figure 1 ). A more focused review determined that the amikacin restriction policy was not being enforced and contributing significantly to increased utilization. It was further determined that amikacin was being used as a first-line drug before sensitivity results were available. Further review of invasive bacterial isolates failed to prove the need for amikacin usage. Educational efforts were successful in decreasing empiric amikacin utilization and significantly lowering amikacin expenditures (Figure 1).

Vancomycin Utilization Guidelines

A slow, steady increase in vancomycin utilization also was observed by the committee. An average of 480 prescriptions were written each quarter over the last 4 years (Figure 2). This information was beneficial when the Centers for Disease Control and Prevention released the Recommendations for Preventing the Spread of Vancomycin Resistance.20 The pharmacy and therapeutics committee formed an ad hoc committee to address prudent vancomycin utilization and draft institution-specific guidelines. Committee membership consisted of representatives from infectious diseases, hematology/oncology, neonatology, nephrology, critical care medicine and pharmacy.

Vancomycin usage subsequently was restricted to the medical staff for empiric therapy for 72 hours. Hospital-specific criteria for continuation of vancomyin therapy beyond 72 hours were drafted by the ad hoc committee and approved by the pharmacy and therapeutics committee and the medical staff executive committee (Table 6).

A vancomycin injection renewal form was used to facilitate implementation of this program. The renewal form contains the criteria for continuation along with an option to discontinue vancomycin therapy. The physician must complete and sign the order form, and a copy is returned to the pharmacy. Results will be monitored and presented to the pharmacy and therapeutics committee each quarter.

ADVERSE DRUG REACTION MONITORING PROGRAM

Vigilance in monitoring, evaluating, and reporting adverse drug reactions is of paramount importance in preventing future adverse events. Assessing a patient's medication regimen when adding additional medications is important to prevent adverse events due to drug interactions. Several reference texts and computer-based programs…

Practicing physicians frequently are confronted with ill-appearing neonates, older infants, and children with signs and symptoms compatible with a serious bacterial infection. The important concepts in the appropriate selection of effective presumptive antibiotic therapy include age- and disease-specific pathogens. Most clinicians are well aware of the most common bacterial causes of sepsis and meningitis in neonates, infants, and children. However, numerous changes in the rank order of these bacterial pathogens, recent descriptions of drug-resistant bacterial pathogens, and the current emphasis on cost-effective management have changed the consideration for appropriate presumptive antibiotic therapy.

Hemophilus influenzae type b, once the most common cause of bacterial meningitis and sepsis in young children, has become a rare pathogen since the widespread use of the conjugate H influenzae type b vaccines.1 The increasing rate of penicillin- and cephalosporin-resistant strains of Streptococcus pneu~ moniae2 has led many clinicians away from the exclusive use of beta-lactam drugs as presumptive therapy for serious bacterial infections in children.3'5 Recent descriptions of Neisseria meningitidis, with variable degrees of resistance to penicillin, have shaken the confidence of physicians in the use of penicillin for meningococcal disease.6

The increase in case descriptions of invasive Streptococcus pyogenes infections, toxic streptococcal syndrome, invasive Staphylococcus aureus infections, and toxic shock syndrome due to S aureus have made the selection of presumptive antibiotic therapy for children with skin and skin structure infections associated with septic shock syndrome more challenging in the 1990s.7 In patients with sepsis seeded from a urinary tract infection, consideration for a variety of gram-negative enteric bacillary organisms and regional susceptibility patterns for Enterobacteriaceae antibiotic therapy and other gram-negative organisms must be taken into consideration in presumptive antibiotic therapy.

Table

TABLE 1Age-Specific Pathogens

TABLE 1

Age-Specific Pathogens

This article focuses on the basic concepts related to the selection of presumptive antibiotic therapy for serious bacterial infections in hospitali2ed children. Sepsis and meningitis will be taken as specific examples of serious bacterial infections to develop the concepts of age- and disease-specific pathogens. The consideration of immunization status, underlying disease, seasonal variability, and age at disease onset will be further developed in the selection of appropriate presumptive antibiotic therapy. Specific therapy based on culture and susceptibility data with a need for antibiotic drug level monitoring will be discussed. The issue of safety versus efficacy will be addressed as it relates specifically to broad-spectrum antibiotic therapy. Finally, presentation of information related to cost analysis, antibiotic and formulary restriction guidelines, formulary costs, drug monitoring programs, adverse drug reaction reporting programs, and selective monitoring and education of physician prescribing habits will serve to focus the clinician's attention on these new and important areas of antibiotic selection in hospitalized children.

AGE-SPECIFIC PATHOGENS

The clinician's initial priority in children with sepsis is to assess perfusion. Clinical findings such as poor capillary refill or skin perfusion, depressed sensorium, hypoxia, acidosis, and oliguria must prompt immediate resuscitation with reestablishment of normal tissue oxygenation. In the 1980s, H influenzae type b was the most common organism responsible for septic shock in young infants; N meningitidis and S pneumoniae frequently caused sepsis among older children and group B streptococcus and Escherichia coli in the infected neonate.8 Any severe bacterial infection can result in hypoperfusion or shock. Hypoperfusion is due to the release of a common cascade of immunologically active substances and is termed systemic inflammatory response syndrome.9 Release of these immunologic mediators is stimulated by bacterial toxins or cell wall constituents.

During resuscitation of patients with systemic inflammatory response syndrome, blood should be obtained for culture, and complete blood cell count, blood glucose, electrolytes, evaluation of coagulation, and liver and renal function should be determined. A sample of urine for analysis and culture, and a chest radiograph also should be obtained. A lumbar puncture should be deferred until the patient's perfusion and vital signs have returned to normal and a thorough physical examination has been performed to evaluate for the presence of increased intracranial pressure. Presumptive antibiotic therapy should be initiated prior to the acquisition of cerebrospinal fluid (CSF) if the lumbar puncture is deferred or delayed. In contrast, if the child is physiologically stable, CSF should be obtained prior to initiating presumptive antibiotics. When cerebrospinal fluid is obtained, it should be analyzed for protein, glucose, cell count/differential, Gram's stain, and culture.

Presumptive antibiotics must be selected following assessment of perfusion and ventilation, and performance of a septic work-up. Selection is based on the concept of age-specific pathogens (Table 1). In the neonate, group B streptococcus and E coli cause most cases of bacterial meningitis and sepsis. In earlyonset sepsis and meningitis, other potential pathogens include Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter diversus, Proteus species, enterococcus, Listeria monocytogenes, other streptococci, and S aureus. Infections caused by H influenzae type b, nontypable H influenzae, S pneumoniae, and N meningitidis, although described, are uncommon. Coagulase-negative staphylococci, other streptococci gram-negative enteric bacilli, and Candida species are important pathogens in premature newborns who remain, for prolonged periods of time, in neonatal intensive care units with invasive intravascular devices. Infection caused by herpes simplex virus should be included in the differential diagnosis of infants with culture-negative sepsis presenting during the first weeks of life. Clinical clues might include a vesicular rash, meningoencephalitis with seizures, or progressive hepatitis.

Following nursery discharge, infants are exposed to multiple individuals colonized in their nasopharynx with common bacterial pathogens such as S pneumoniae, N meningitidis, and H influenzae type b, and these pathogens become the most frequent causes of bacterial sepsis and meningitis. However, until approximately 3 months of age, some neonatal pathogens (Table I) can cause both sepsis and meningitis. Therefore, in the patient category previously designated "older infant,"10 neonatal and childhood bacterial pathogens must be considered in selecting presumptive antibiotic therapy. Streptococcus pneumoniae and N meningitidis are the two most common causes of bacterial sepsis and meningitis in children older than 3 months (Table 1 ). The infant who has received all of the primary immunization series has benefited from a significant reduction of H influenzae type b infections.1 Children older than 12 to 15 months who have received a booster dose of conjugate H influenzae type b vaccine also find this pathogen to be uncommon.

Table

TABLE 2Presumptive Antibiotic Therapy

TABLE 2

Presumptive Antibiotic Therapy

In older infants and children with skin, skin structure, bone and joint, or pulmonary infection associated with sepsis or meningitis, S aureus and S pyogenes must be considered.7 These pathogens also must be considered in children with a toxic shock-like syndrome, and antibiotics active against S pyogenes and S aureus should be prescribed. Staphylococcus aureus may occur in older children and adolescents without a focus; two reports have described severe staphylococcal sepsis in 9 and 15 previously healthy patients.11,12 However, even in these reports, 7 out of 9 had bone/joint infections and 8 out of 9 had multiple pulmonary infiltrates. Thirteen out of 15 had cutaneous manifestations of infection with sepsis, respectively. In these older patients with suggestive findings, antistaphylococcal presumptive therapy should be included.

PRESUMPTIVE ANTIBIOTIC THERAPY

In addition to the age of the patient and specific type of infection, selection of appropriate presumptive antibiotic therapy must consider drug-allergy history, antibiotic pharmacokinetics and pharmacodynamics, anticipated susceptibility of pathogens, safety, and cost. The primary antibiotics or antibiotic combinations for consideration, as well as alternatives, should be guided by these parameters (Table 2).

The synergistic combination of ampicillin and gentamicin is indicated for neonates with gram-positive cocci in chains in CSF because of the probability these will be group B streptococcus. Ampicillin and gentamicin or cefotaxime is appropriate for neonates with suspect meningitis. When a cephalosporin is prescribed, ampicillin is necessary to provide activity against Enterococcus and L monocytogenes. Vancomycin is an alternative to ampicillin, especially if multiply resistant S aureus or coagulase-negative staphylococcal infections are documented or likely. In the older infant (from the time of leaving the nursery until approximately 3 months of age), the combination of ampicillin and cefotaxime is an appropriate antibiotic regimen for presumptive therapy in sepsis and meningitis.

Until recently, cefotaxime or ceftriaxone was appropriate for older children with suspected sepsis or meningitis.4 However, because of increasing resistance of S pneumoniae to penicillin and cephalosporins, most experts consider vancomycin plus a third-generation cephalosporin to be the antibiotic regimen of choice for suspected bacterial meningitis. As noted in Table 3, the appropriate dose of vancomycin in the treatment of children with bacterial meningitis is 60 mg/kg/day divided in an every 6-hour regimen.

In cases of invasive bacterial disease without meningitis, high doses of cephalosporins (cefotaxime 75 mg/kg/dose every 8 hours or ceftriaxone 50 mg/kg/dose every 12 hours) may be used as empiric therapy (Table 3).12,13 Alternative drugs include clindamycin, imipenem, meropenem (Merrem; soon to be released), or in patients older than 18 years, a fluoroquinolone antibiotic.

Table

TABLE 3Antibiotic Doses in Presumptive Antibiotic Therapy*

TABLE 3

Antibiotic Doses in Presumptive Antibiotic Therapy*

SPECIFIC THERAPY

Definitive antibiotic therapy is determined by identification and antibiotic susceptibility of the invasive isolate. Organisms such as H influenzae type b, nontypable H infuenzae, M catanhalis, and Enterococcus may produce beta-lactamase enzymes necessitating the use of non-beta- lactam drugs. The specific minimum inhibitory concentrations (MICs) of S pneumoniae for penicillin (intermediate-resistance =0.1 to 1.0 mg/mL or high-level resistance 5*2 mg/mL) and cephalosporins (cefotaxime-intermediate resistance =0.5 mg/mL, or high-level resistance >1 mg/mL) determine which antibiotics are appropriate.13,14 In cases of meningitis, any level of resistance to penicillin or cephalosporin should preclude the selection of those agents as monotherapy. Continuation of vancomycin plus a third-generation cephalosporin, with or without rifampin, is indicated. In nonmeningitis, higher-dose penicillin, cephalosporins, or alternative drugs (such as clindamycin) can be used successfully in the treatment of infections caused by intermediately drug-resistant pneumococcus.

In meningococcal disease, the drug of choice remains parenteral penicillin. However, third-generation cephalosporins are recommended by some experts because they may eradicate nasopharyngeal colonization with N meningitidis,15 eliminating the need for rifampin chemoprophylaxis at the end of therapy.16 Clindamycin, or clindamycin plus penicillin, are recommended for the therapy of necrotizing fasciitis or other deep-seeded infections caused by group A streptococci. For invasive infections caused by methicillin-sensitive S aureus, the use of a semisynthetic penicillin such as nafcillin or a first-generation cephalosporin such as cefazolin is appropriate.

Parenteral clindamycin is a suitable alternative. Vancomycin is indicated for therapy of infections caused by methicillin-resistant strains of S aureus. Patients with meningitis caused by drug-resistant strains of S pneumoniae should have a repeat lumbar puncture performed 24 to 48 hours after initiation of therapy to evaluate the cerebrospinal fluid for continued growth of the organism. If the cerebrospinal fluid is sterile, continuation of initial therapy is appropriate. If S pneumoniae persists in the cerebrospinal fluid after 24 to 48 hours, the addition of rifampin should be considered. A repeat lumbar puncture 24 to 48 hours after adding rifampin should be performed.

OTHER SERIOUS BACTERIAL INFECTIONS

Presumptive therapy for other serious bacterial infections in hospitalized children adheres to the same principles of age- and disease-specific pathogens (Table 4). Other considerations include:

* site of infection,

* host immune response,

* high-risk host factors, foreign bodies, and underlying disease, and

* regional or local antibiotic susceptibility profiles.

COST ANALYSIS OF PRESUMPTIVE ANTIBIOTIC THERAPY

Efficacy, safety, and cost are key factors that should be considered in the selection of antibiotic therapy. 3 Cost is an especially important consideration when safety and efficacy are equivalent. The cost analysis of appropriate presumptive antibiotic therapy should include an evaluation of the actual acquisition cost of the regimen along with associated institutional or unrecognized costs. Acquisition costs may vary tremendously among institutions, and information pertaining to the actual acquisition cost is considered proprietary by most institutions. Associated institutional costs of the presumptive antibiotic regimen include associated costs of drug administration and the costs associated with obtaining pharmacokinetic drug levels. Frequent drug level monitoring of a regimen can add a significant, often unrecognized, expense to the cost of a regimen.

Table

TABLE 4Recommended Presumptive Therapy of Suspected Nonviral Infections in Previously Normal Hospitalized Infants and Children

TABLE 4

Recommended Presumptive Therapy of Suspected Nonviral Infections in Previously Normal Hospitalized Infants and Children

A cost comparison of presumptive antibiotic therapy for meningitis in older children is presented in Table 5. The total daily institutional costs, based on average wholesale price (AWP), are presented as monotherapy regimens with the broad-spectrum cephalosporins, cefotaxime and ceftriaxone. The cost associated with the addition of vancomycin to both regimens also is presented.

Table

TABLE 5Cost Analysis of Presumptive Therapy in Older Children*

TABLE 5

Cost Analysis of Presumptive Therapy in Older Children*

Table

TABLE 6Vancomycin Injection Renewal Criteria

TABLE 6

Vancomycin Injection Renewal Criteria

FORMULARY COSTS

Excessive and inappropriate antimicrobial utilization increases the potential for development of resistant organisms, exposes patients to potential risk of adverse reactions, and increases drug expenditures. Cost containment has taken on an added significance in the current health-care climate as antimicrobial agents account for a significant portion of most drug formulary budgets. Antibiotic expenditures average 15% to 20% of the monthly drug budget at our institution. Practitioners must effectively manage the rapid emergence of resistant organisms in the face of mandates to reduce and control drug expenditures.

It is imperative to have an organized plan in place to routinely evaluate the antimicrobial formulary, antimicrobial utilization trends, and bacterial resistance patterns. This plan should be a collaborative, multidisciplinary effort between the infectious disease service, pharmacy and microbiology departments, and pharmacy and therapeutics committee. Communication between these services can result in increased effectiveness along with lowering the cost of therapy and inventory.21

Rapid culture identification and sensitivity reporting represent another opportunity to streamline patient therapy and decrease antimicrobial expenditures. Timely communication of this information from the clinical microbiology department to the pharmacy department is instrumental in achieving this goal. Computerized databases with inter-relational capabilities have streamlined this check and balance process.

As new antimicrobial agents become available, the formulary should be evaluated completely for therapeutic duplication. Every effort should be made to have a limited number of effective agents available in each therapeutic class.

DRUG MONITORING PROGRAM AND DRUG LEVEL MONITORING

The need for frequent drug level monitoring can add significantly to institutional expenses. Therapeutic drug monitoring programs establish guidelines for appropriate drug use, guidelines for drug level monitoring, monitoring for adverse drug events, and consultation of drug interactions, cost, and safety. Therapeutic drug monitoring programs can decrease the number of drug levels obtained, significantly shorten length of hospitalization, obtain more optimal therapeutic aminoglycoside serum levels, and decrease the incidence of nephrotoxicity. Each dollar spent by a therapeutic drug monitoring service has been demonstrated to result in a $30 savings.18

A review of drug level ordering practices at our institution revealed that orders to check levels are usually written at the time of initial prescribing. A collaborative initiative between the clinical pharmacology department, the pharmacy department, and medical staff is being undertaken to decrease the routine ordering of antimicrobial drug levels during the first 72 hours of presumptive therapy provided age-specific recommended doses are used. Drug levels are recommended during the first 72 hours only for patients meeting one of the following high-risk criteria:

Figure 1. Quarterly amikacin utilization trends, 1993 to 1995.

Figure 1. Quarterly amikacin utilization trends, 1993 to 1995.

Figure 2. Quarterly vancomycin injection utilization, 1992 to 1995.

Figure 2. Quarterly vancomycin injection utilization, 1992 to 1995.

* intensive care unit patient,

* <3 months of age when therapy is expected to exceed 72 hours,

* renal insufficiency,

* concomitant use of other nephrotoxic drugs,

* central nervous system infections, and e altered body composition.

The goals of this program are to aid physicians in dosing antimicrobials with a narrow therapeutic margin and allow cost savings for the institution.

ANTIBIOTIC RESTRICTION GUIDELINES

Antibiotic restriction guidelines are an effective method of preserving an antibiotic for use in patients with resistant organisms and limiting the use of costly agents when less expensive alternatives are available and appropriate.19 Use of certain antibiotics can be restricted to specific services or limited to use in patients with specific diseases. For example, at our institution, gentamicin and tobramycin are available to any physician. However, to control costs and preserve the usefulness of amikacin for patients with organisms that are resistant to other aminoglycosides, amikacin can only be used if approved by the infectious disease service.

Antimicrobial utilization trends over time are also beneficial in formulary management decisions. The pharmacy and therapeutics committee of our institution reviews antimicrobial utilization patterns each quarter. Utilization patterns are separated by therapeutic class and include the number of prescriptions written, the number of doses dispensed, and institutional acquisition expenditures of each agent used in the therapeutic class. Sudden increases or changes in utilization can be identified. If necessary, more focused reviews can be undertaken to further analyze the trend and identify strategies to improve utilization guidelines. Physician feedback and education are critical elements of these reviews.

Amikacin Restriction Guidelines

A significant increase in the utilization of amikacin in 1993 was noted during the regular reviews presented to the pharmacy and thetapeutics committee (Figure 1 ). A more focused review determined that the amikacin restriction policy was not being enforced and contributing significantly to increased utilization. It was further determined that amikacin was being used as a first-line drug before sensitivity results were available. Further review of invasive bacterial isolates failed to prove the need for amikacin usage. Educational efforts were successful in decreasing empiric amikacin utilization and significantly lowering amikacin expenditures (Figure 1).

Vancomycin Utilization Guidelines

A slow, steady increase in vancomycin utilization also was observed by the committee. An average of 480 prescriptions were written each quarter over the last 4 years (Figure 2). This information was beneficial when the Centers for Disease Control and Prevention released the Recommendations for Preventing the Spread of Vancomycin Resistance.20 The pharmacy and therapeutics committee formed an ad hoc committee to address prudent vancomycin utilization and draft institution-specific guidelines. Committee membership consisted of representatives from infectious diseases, hematology/oncology, neonatology, nephrology, critical care medicine and pharmacy.

Vancomycin usage subsequently was restricted to the medical staff for empiric therapy for 72 hours. Hospital-specific criteria for continuation of vancomyin therapy beyond 72 hours were drafted by the ad hoc committee and approved by the pharmacy and therapeutics committee and the medical staff executive committee (Table 6).

A vancomycin injection renewal form was used to facilitate implementation of this program. The renewal form contains the criteria for continuation along with an option to discontinue vancomycin therapy. The physician must complete and sign the order form, and a copy is returned to the pharmacy. Results will be monitored and presented to the pharmacy and therapeutics committee each quarter.

ADVERSE DRUG REACTION MONITORING PROGRAM

Vigilance in monitoring, evaluating, and reporting adverse drug reactions is of paramount importance in preventing future adverse events. Assessing a patient's medication regimen when adding additional medications is important to prevent adverse events due to drug interactions. Several reference texts and computer-based programs are available to help facilitate this process. The Joint Commission on the Accreditation of Healthcare Organizations requires hospitals to have a formalized system in place for collecting and reporting adverse drug reactions.

Adverse drug reaction rates cited in the literature are reported to occur in 10% to 20% of hospitalized patients.22 Antibiotics are among the most frequent agents that cause adverse events. Prior to FDA approval, safety and efficacy studies attempt to identify the adverse event profile of a medication. However, the true adverse event profile is known only after widespread use and experience in multiple patient populations.23 Reporting adverse events is a key component of identifying the true adverse event profile of a medication and subsequent additions or changes in the product labeling. These reports are also important educational tools for the medical staff.

CONCLUSIONS

The appropriate use of presumptive antibiotic therapy in the hospitalized child with sepsis and meningitis is determined by the age of the host and specific site of infection. Season, underlying diseases, associated organ or organ system involvement, and clinical presentation may modify the rank order of possible pathogens. The selection of presumptive antibiotics also must take into account local drug resistance patterns and the effect of current immunization programs on the incidence of specific organisms. Finally, the consideration in the 1990s for a cost-effectiveness analysis of presumptive antibiotic therapy with the proper use of drug monitoring programs, antibiotic restriction guidelines, and adverse drug reaction reporting are mandatory for the effective and most financially-appropriate presumptive antibiotic regimens.

REFERENCES

1. Adams WO, Deaver KA, Cochi SL, et al. Decline of childhood Haemophilus influenzae type b (HIB) disease in the Hib vaccine era. JAtAA. 1993;269:221-226.

2. Schutze GE, Kaplan SL, Jacobs RF. Resistant pneumococcus: a worldwide problem. Infection. 1994;22:233-237.

3. Tan TQ, Schutze GE, Mason EO Jr, et al. Antibiotic therapy and acute outcome of meningitis due to Streptococcus pneumoniae considered intermediately susceptible to broad spectrum cephalosporins. Antmucrob Agents Chemother. 1994:38:918· 923.

4. McCtacken GH, Nelson JD, Kaplan SL, « al. Consensus report·, antimicrobial therapy for bacterial meningitis in infants and children. Pediatr Infect Dis J. 1987;6:501-505.

5. Friedland IR1 McCracken GH Jr. Management of infections caused by antibioticresistant Streptococcus pneumoniae. N Engl/ Med. 1994;331:377-382.

6. Woods CR, Givner LB. Drug-resistant meningococcal infections. Sem Pediatr infect Dis. 1996;7:204-221.

7. Committee on Infectious Diseases, American Academy of Pediatrics. Staphylococcal food poisoning. In: Red Book. Elk Grove Village, 111: American Academy of Pediatrics; 1994:428-439.

8. Jacobs RF, Sowell MK, Moss MM, et al. Septic shock in children: bacterial etiologies and temporal relationships. Pediatr Infect Dis J. 1990;9:196-200.

9. Darvllle T, Giroir B. Jacobs R. The systemic inflammatory response syndrome (SIRSV. immunology and potential immunotherapy. lv\f«cBcm. 1993-.2UZ79-WO.

10. Baumgartner ET, Augustine RA, Steele RW. Bacterial meningitis in older neonates. Am J Dis Child. 1983;137:1052-1054.

11. Shulman ST1 Ayoub EM. Severe staphylococcal sepsis in adolescents. Pediatrics. 1976;58:59-66.

12. Hieber P, Nelson AJ, McCracken GH Jr. Acute disseminated staphylococcal disease in childhood. AmJ Dis Child. 1977;131:181-185.

13. Darvllle T, Jacobs RF, Trang JM, et al. Pharmacokinetic evidence supporting an 8hour administration interval (or cefotaxime in infants and children. Clmictfl Drug imitigation. 1995;9:206-211.

14. Jacobs RF, Kaplan SL, Schutte GE, et al, Relationship of MlCs to efficacy of cefotaxime in treatment of Streptococcus pneumoniae infections. Anumicrob Agents Chemother. 1996;40:895-898.

15. Goldwater PN. Effect of cefotaxime oi ceftriaxone treatment on nasopharyngeal Haemophilus influenzae type b colonization in children. Antmucrofc Agents Chemother. 1995;39:2150-2152.

16. Schwartz B, Al-Tobaiqi A, Al-Ruwais A, et al. Comparative efficacy of ceftriaxone and rifampicln in eradicating pharyngeal carriage of group A Neisseria meningitis. Lancet. 1988;1:1239-1242.

17. Jacobs RF, Darville T, Parks JA, et al. Safety profile and efficacy of cefotaxime for the treatment of hospitalized children. CIm Infect Dis. 1992;14:56-65.

18. Destache CJ. Clinical and economic benefits of a clinical pharmacokinetic service: 1987 versus 1992 data. Medico/ Interface. 1994;7:84-90.

19. Shulkin DJ. Enhancing the role of physicians in the cost-effective use of pharmaceuticals. Hospital Formular)!. 1994;29:262-273.

20. Centers for Disease Control and Prevention. Recommendations for preventing the spread of vancomycin resistance, MMWR Morb Morto/ Wkrj Re|>. September 22, 1995:44(RR-12);1-13.

21. Schentag JJ, Ballow CH, Fritz AL. Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory. Diagn Microbiol Infect Dis. 1993;16:255-264.

22. Orsini MJ, Funk PA, Thorn DB. An ADR surveillance program: increasing quality, number of incidence reports. Formulary. 1995;30:454-461.

23. May JR, Adverse drug reactions and interactions. In: DlPiro JT, Talbert RL, Hayes PE, et al, eds. Pharmacodterapy: A Pathophysiologic Approach. 2nd ed. New York, NY: Elsevier; 1992:71-83.

TABLE 1

Age-Specific Pathogens

TABLE 2

Presumptive Antibiotic Therapy

TABLE 3

Antibiotic Doses in Presumptive Antibiotic Therapy*

TABLE 4

Recommended Presumptive Therapy of Suspected Nonviral Infections in Previously Normal Hospitalized Infants and Children

TABLE 5

Cost Analysis of Presumptive Therapy in Older Children*

TABLE 6

Vancomycin Injection Renewal Criteria

10.3928/0090-4481-19961101-09

Sign up to receive

Journal E-contents