antibiotik therapy nelson

7/28/2019 Antibiotik Therapy Nelson

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Kliegman: Nelson Textbook of Pediatrics,

18th ed.

Copyright 2007 Saunders, An Imprint of Elsevier

Section 3Antibiotic Therapy

Chapter 179Principles of Antibacterial TherapyMark R. Schleiss

Antibacterial therapy in infants and children presents many challenges. For some agents there isa paucity of pediatric data regarding pharmacokinetics and optimal dosages; pediatric

recommendations are extrapolated from studies in adults. The clinician must consider importantdifferences among various age groups of the pathogenic species responsible for pediatric

bacterial infections; age-appropriate antibiotic dosing and toxicities must also be considered.

Specific antibiotic therapy is optimally driven by a microbiologic diagnosis, such as isolation of

the pathogenic organism from a sterile body site, and supported by antimicrobial susceptibilitytesting. Much of pediatric infectious diseases practice is based on a clinical diagnosis with

empirical use of antibacterial agents before or even without eventual identification of the

specific pathogen.

Several key considerations must be incorporated in decisions about the appropriate empirical use

of antibacterial agents in infants and children. It is important to know the age-appropriate

differential diagnosis with respect to likely pathogens. This affects the choice of antimicrobialagent and also the dose, dosing interval, and route of administration (oral vs parenteral). A

complete history and physical examination combined with appropriate laboratory andradiographic studies are necessary to identify specific diagnoses, which in turn affects the choice,

dosing, and urgency of administration of antimicrobial agents. The vaccination history may

reflect reduced risk, but not necessarily elimination of risk, for diseases for which the vaccination

series has been completed. The risk for infections is greatly affected by the immunologic status,which may be compromised by immaturity (neonates), underlying disease, and associated

treatments (see Chapter 177 ). Infections in immunocompromised children often result from

bacteria that are not considered pathogenic in immunocompetent children. The presence of

foreign bodies also increases the risk of bacterial infections (see Chapter 178 ). The likelihood of

central nervous system (CNS) involvement must be considered because many bacteremicinfections in childhood, includingHaemophilus influenzae type b, pneumococcus, and

meningococcus, carry a significant risk for hematogenous spread to the CNS.

The patterns ofantimicrobial resistance in the community, and for the potential causative

pathogen being empirically treated, must also be considered. Resistance to penicillin andcephalosporin antibiotics is now commonplace among strains ofStreptococcus pneumoniae,

often necessitating the use of other classes of antibiotics. The striking emergence of community-


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acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has further complicated

antibiotic choices.

Antimicrobial resistance occurs through many modifications of the bacterial genome (Tables

179-1 and 179-2 [1] [2]). Mechanisms include enzyme inactivation of the antibiotic, decreased

cell membrane permeability to intracellularly active antibiotics, efflux of antibiotics out of thebacteria, protection or alteration of the antibiotic target site, excessive production of the target

site, or passing the antimicrobial site of action.

Antibiotic action is related to achieving therapeutic levels at the site of infection. Although

measuring the level of antibiotic at the site of infection is not always possible, one may measure

the serum level and use it as a surrogate target to achieve the desired effect at the tissue level.Various target serum levels are appropriate for different antibiotic agents and are assessed by the

peak and trough serum levels, and the area under the therapeutic drug level curve ( Fig. 179-1 ).

These levels are in turn a reflection of the route of administration, drug absorption (IM, PO),

volume of distribution, and drug elimination half-life, as well as of drug-drug interactions that

might enhance or impede enzymatic inactivation of an antibiotic or result in antimicrobialsynergism or antagonism ( Fig. 179-2 ).

TABLE 179-1 -- Mechanisms of Resistance to -Lactam Antibiotics

I. Alter target site (PBP, penicillin-binding protein)

A. Decrease affinity of PBP for -lactam antibiotic

1. Modify existing PBP

a. Create mosaic PBP

Insert nucleotides obtained from neighboring bacteria, e.g.,penicillin-resistant Streptococcus pneumoniae

Mutate structural gene of PBP(s), e.g., ampicillin-resistant

-lactamase-negativeHaemophilus influenzae

2. Import new PBP, e.g., mecA in methicillin-resistant Staphylococcusaureus

II. Destroy -lactam antibiotic

A. Increase production of -lactamase

1. Acquire more efficient promoter

a. Mutate existing promoter

b. Import new one

2. Deregulate control of -lactamase production

a. Mutate regulator genes, e.g., ampDin stably derepressed

Enterobacter cloacae


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B. Modify structure of resident -lactamase

1. Mutate its structural gene, e.g., extended-spectrum -lactamases inKlebsiellapneumoniae

C. Import new -lactamase(s) with different spectrum of activity

III. Decrease concentration of -lactam antibiotic inside cell

A. Restrict its entry (loss of porins)

B. Pump it out (efflux mechanisms)

TABLE 179-2 -- Aminoglycoside-Modifying Enzymes

ENZYMES USUAL ANTIBIOTICS MODIFIED COMMON GENERA

Phosphorylation

APH(2) K, T, G SA, SR

APH(3)-I K E, PS, SA, SR

APH(3)-III K, A E, PS, SA, SR

Acetylation

AAC(2) G PR

AAC(3)-I T, G E, PS

AAC(3)-III, -IV, OR-V K, T, G E, PS

AAC(6) K, T, A E, PS, SAAdenylation

ANT(2) K, T, GE, PS

ANT(4) K, T, A SA

A, amikacin; AAC, aminoglycoside acetyltransferase; ANT, aminoglycoside

nucleotidyltransferase; APH, aminoglycoside phosphotransferase;

E, Enterobacteriaceae; G, gentamicin; K, karamycin; PR,Providencia-Proteus; PS,

pseudomonids; SA, staphylococci; SR, streptococci; T, tobramycin.

AGE- AND RISK-SPECIFIC USE OF ANTIBIOTICS IN CHILDREN.Neonates.

The causative pathogens of neonatal infections are typically acquired around the time of

delivery. Thus, empiric antibiotic selection must take into account the importance of thesepathogens in neonates (see Chapter 109 ). Among the causes of neonatal sepsis in infants, group


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B streptococcus is the most common, although intrapartum antibiotic prophylaxis has greatly

decreased the incidence of this infection (see Chapter 183 ). Gram-negative enteric organisms

acquired from the maternal birth canal, in particularEscherichia coli, are other common causesof neonatal sepsis. Although rare,Listeria monocytogenes is also an important pathogen, and is

resistant to cephalosporin antibiotics. All of these organisms can be associated with meningitis in

the neonate; therefore, if meningitis cannot be excluded, antibiotic management should includeagents capable of crossing the blood-brain barrier.

Older Children.

Antibiotic choices in toddlers and young children were once driven by the unique susceptibilityof this age group to invasive disease caused byH. influenzae type b (see Chapter 192 ). With the

advent of conjugate vaccines forH. influenzae type b, invasive disease has declined dramatically.

It is still appropriate to consider the use of antimicrobials that are active against this pathogen,

particularly if meningitis is a consideration. Other particularly important pathogens to beconsidered in this age group include S. pneumoniae, meningococcus, and S. aureus.

Antimicrobial resistance is commonly exhibited by S. pneumoniae and S. aureus. Strains ofS.pneumoniae that are resistant to penicillin and cephalosporin antibiotics are frequentlyencountered in clinical practice. Similarly, MRSAs are highly prevalent in many regions.

Resistance ofS. pneumoniae as well as MRSA is due to mutations that confer alterations in

penicillin binding proteins, the molecular targets of penicillin and cephalosporin activity (seeTable 179-1 ).

Depending on the specific diagnosis, other pathogens that are commonly encountered amongolder children includeMoraxella catarrhalis, nontypable strains ofH. influenzae, and

Mycoplasma pneumoniae, which cause otorhinolaryngologic infections and pneumonia; group A

streptococcus, which causes pharyngitis, skin and soft tissue infections, osteomyelitis, and septic

arthritis;Kingella kingae, which causes bone and joint infections; viridans streptococci andEnterococcus, which cause endocarditis; and Salmonella, which causes enteritis, bacteremia,

osteomyelitis, and septic arthritis. This complexity underscores the importance of formulation of

a clear clinical diagnosis, including an assessment of the severity of the infection, in concert withknowledge of local susceptibility patterns in the community.

Immunocompromised and Hospitalized Patients.

It is important to consider the risks associated with immunocompromising conditions(malignancy, solid organ, or hematopoietic stem cell transplantation) or with settings where

prolonged hospitalization predisposes to nosocomial infections (intensive care, burns). In

addition to the usual bacterial pathogens,Pseudomonas aeruginosa and enteric organisms,includingEscherichia coli, Klebsiella pneumoniae, Enterobacter, and Serratia, are important

considerations as opportunistic pathogens in these settings. Selection of appropriate

antimicrobials is challenging because of the diverse causes and scope of antimicrobial resistanceexhibited by these organisms. Many strains of enteric organisms have resistance due to extended

spectrum -lactamases (ESBLs) (see Table 179-1 ).P. aeruginosa encodes proteins that function

as efflux pumps to eliminate multiple classes of antimicrobials from the cytoplasm orperiplasmic space. In addition to these gram-negative pathogens, infections caused by


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Enterococcus, bothE. faecalis andE. faecium, are inherently difficult to treat. These organisms

may cause urinary tract infection or infective endocarditis in immunocompetent children, and

may be responsible for a variety of syndromes in immunocompromised patients, especially in thesetting of prolonged intensive care. The occurrence of strains ofvancomycin-resistant

Enterococcus (VRE) has further complicated antimicrobial selection in high-risk patients, and

has necessitated the development of newer antimicrobials that target these highly resistant gram-positive infections, although experience with many of these newer agents in the management ofcomplex hospitalized pediatric patients is limited.

Infections Associated with Medical Devices.

A special situation affecting antibiotic use is the presence of an indwelling medical device, suchas a venous catheter, ventriculoperitoneal shunt, stent, or other catheter (see Chapter 178 ). In

addition to S. aureus, coagulase-negative staphylococci are also a major consideration.

Coagulase-negative staphylococci seldom cause serious disease without a risk factor such as anindwelling catheter. Empiric antibiotic regimens must take this risk into consideration. In

addition to appropriate antibiotic therapy, removal or replacement of the colonized prostheticmaterial is commonly required for cure.

ANTIBIOTICS COMMONLY USED IN PEDIATRIC PRACTICE ( TABLE 179-3 )Penicillins.

Although there has been ever-increasing emergence of resistance to penicillins, these agents

remain valuable and are commonly used for management of many pediatric infectious diseases.

TABLE 179-3 -- Antibacterial Medications (Antibiotics)

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS(MECHANISM OF

ACTION) AND DOSING COMMENTS

Amikacin sulfate

Amikin.

Injection: 50 mg/mL, 250mg/ml.

Aminoglycoside

antibiotic active

against gram-negative

bacilli, especially

Escheri chia coli ,

Kl ebsiell a, Proteus,

Enterobacter, Serr atia,

and Pseudomonas.Neonates: Postnatal age

7 days: 1,2002,000

g: 7.5 mg/kg q 1218hr IV or IM; >2,000 g:

10 mg/kg q 12 hr IV or

IM;postnatal age >7

Cautions: Anaerobes,Streptococcus (including

S. pneumoniae) are

resistant. May causeototoxicity and

nephrotoxicity. Monitor

renal function. Drug

eliminated renally.

Administered IV over3060 min.

Drug interactions: Maypotentiate other ototoxic

and nephrotoxic drugs.

Target serum


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


days: 1,2002,000 g IV

or IM:

7.5 mg/kg q 812 hr IVor IM; >2,000 g: 10

mg/kg q 8 hr IV or IM.

Children: 1525mg/kg/24 hr divided q

812 hr IV or IM.

Adults: 15 mg/kg 24 hr

divided q 812 hr IV orIM.

concentrations: Peak 25

40 mg/L;trough


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Suspension: 125 mg/5 mL,

200 mg/5 mL, 250 mg/5

mL, 400 mg/5 mL.

producing bacteria. S.

aureus(notmethicillin-resistant

organism),

Streptococcus,

Haemophilus

infl uenzae, Moraxell a

catarrhall s, E. coli,

Kl ebsiell a, Bacteroides

fragilis.

Neonates: 30 mg/kg/24hr divided q 12 hr PO.

Children: 2045 mg/kg

24 hr divided q 812 hrPO. Higher dose 8090

mg/kg/24 hr PO for

otitis media.

Comment: Higher dose

may be active against

penicillintolerant/resistant S.

pneumoniae.

Ampicillin

Polycillin, Omnipen.

Capsule: 250,500 mg.

Suspension: 125 mg/5 mL,250 mg/5 mL, 500 mg/5mL.

Injection.

-Lactam with same

spectrum of

antibacterial activity

as amoxicillin.

Neonates: Postnatal age7 days 2,000 g: 50

mg/kg/24 hr IV or IM q

12 hr (meningitis: 100mg/kg/24 hr divided q

12 hr IV or IM); >2,000

g: 75 mg/kg/24 hr

divided q

8 hr IV or IM

(meningitis: 150

mg/kg/24 hr divided q8 hr IV or IM).Postnatal age

>7 days


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


12 hr IV or IM);1,200

2,000 g: 75 mg/kg/24

hr divided q 8 hr IV orIM (meningitis: 150

mg/kg/24 hr divided q

8 hr IV or IM); >2,000

g: 100 mg/kg/24 hrdivided q 6 hr IV or IM

(meningitis: 200


6 hr IV or IM).

Children: 100200

mg/kg/24 hr divided q6 hr IV or IM(meningitis: 200400


46 hr IV or IM).

Adults: 250500 mg q

48 hr IV or IM.

Ampicillin-sulbactam

Unasyn.

Injection.

-Lactam (ampicillin)

-lactamase inhibitor

(sulbactam) enhances

ampicillin activityagainst penicillinase-

producing bacteria:

S. aur eus,

Streptococcus, H.

infl uenzae, M .

catarrhali s, E. coli,

Klebsiella, B. fr agili s.

Children: 100200


48 hr IV or IM.

Adults: 12 g q 68 hr

IV or IM (max dailydose: 8 g).

Cautions: Drug dosed on

ampicillin component.

May cause diarrhea, rash.

Drug eliminated renally.

Note: Higher dose may

be active againstpenicillin-

tolerant/resistant S.

pneumoniae.

Drug interaction:

Probenecid.

Azithromycin Azalide antibioticwith activity against

Note: very long half-life

permitting once-daily dosing.


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Zithromax.

Tablet: 250 mg.

Suspension: 100 mg/5 mL,200 mg/5 mL.

S. aur eus,

Streptococcus, H.

influenzae,

Mycoplasma,

Legionella, Chlamydia

trachomatis.

Children: 10 mg/kg POon day 1 (max: 500 mg)

followed by 5 mg/kg

PO q 24 hr for

4 days.

Group A Streptococcuspharyngitis: 12

mg/kg/24 hr PO (max:500 mg) for 5 days.

Adults: 500 mg PO day

1 followed by 250 mgfor 4 days.

Uncomplicated C.

trachomatis infection:

single 1 g dose PO.

No metabolic-based drug

interactions (unlike

erythomycin andclarithromycin), limited

gastrointestinal distress.

Shorter-course regimens (e.g.,

13 days) under investigation.Three-day, therapy (10

mg/kg/increasing frequency

(not for streptococcus

pharyngitis).

Aztreonam

Azactam.

Injection.

-Lactam

(monobactam)

antibiotic with activity


aerobic bacteria,

Enterobacteriaceae,

and Pseudomonas

aeruginosa.

Neonates: Postnatal age

7 days 2,000 g: 60

mg/kg/24 hr divided q12 hr IV or IM;

>2,000 g: 90 mg/kg/24

hr divided q 8 hr IV or

IM;postnatal age >7days


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


12 hr IV or IM; 1,200

2,000 g: 90 mg/kg/24

hr divided q 8 hr IV orIM; >2,000 g: 120


68 hr IV or IM.

Children: 90120


68 hr IV or IM. For

cystic fibrosis up to 200mg/kg/24 hr IV.

Adults: 12 g IV or IM

q 812 hr (max 8 g/24hr).

Carbenicillin

Geopen Injection.

Geocillin oral tablet.

Extended-spectrum

penicillin (remains

susceptible to

penicillinase

destruction) active

against Enterobacter,

indole-positive

Proteus, andPseudomonas.


7 days 2,000 g: 225mg/kg/24 hr divided q

8 hr IV or IM; >2,000

g: 300 mg/kg/24 hrdivided q 6 hr IV or

IM; >7 days: 300400


6 hr IV or IM.

Children: 400600


46 hr IV or IM.

Cautions: Painful givenintramuscularly;

rash;each gram contains

5.3 mEq sodium.Interferes with platelet

aggregation at high

doses, increases in liver

transaminase levels.

Renally eliminated.

Oral tablet for treatment

of urinary tract infectiononly.

Drug interaction:

Probenecid.

Cefaclor

Ceclor.

2nd generation

cephalosporin active

against S. aureus,

Cautions:-Lactamsafety profile (rash,

eosinophilia) with high


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF



Suspension: 125 mg/5 mL,187 mg/5 mL, 250 mg/5mL, 375 mg/5 mL.

Streptococcus

includingS.

pneumoniae, H .

in f luenzae, E. coli,

Klebsiella, and

Proteus.


812 hr PO (max dose:

2 g).

Adults: 250500 mg q68 hr PO.

incidence of serumsickness reaction.

Renally eliminated.

Drug interaction:Probenecid.

Cefadroxil

Duricef, Ultracef.

Capsule: 500 mg.

Tablet: 1,000 mg.


250 mg/5 mL, 500 mg/5mL.

First-generation


against S. aureus,

Streptococcus, E. coli ,

Klebsiella, and

Proteus.

Children: 30 mg/kg/24hr divided q 12 hr PO

(max dose: 2 g).

Adults: 250500 mg q812 hr PO.

Cautions:-Lactam

safety profile (rash,

eosinophilia). Renally

eliminated. Long half-lifepermits q 1224 hr

dosing.


Cefazolin

Ancef, Kefzol.

Injection.

1st generation


against S. aureus,


Klebsiella, and

Proteus.


7 days 40 mg/kg/24 hrdivided q 12 hr IV or

IM; >7 days 4060

mg/kg/24 hr divided q8 hr IV or IM.

Children: 50100


Caution:-Lactam safetyprofile (rash,


eliminated. Does notadequately penetrate

CNS.

Drug interaction:

Probenecid.


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


8 hr IV or IM.

Adults: 0.52 g q 8 hrIV or IM (max dose: 12g/24 hr).

Cefdinir

Omnicef.

Capsule: 300 mg.

Oral suspension: 125 mg/5mL.

Extended-spectrum,

semi-synthetic

cephalosporin.

Children 6 mo12 yr:14 mg/kg/24 hr in 1 or

2 doses PO (max: 600

mg/24 hr).

Adults: 600 mg q 24 hr

PO.

Cautions: Reduce dosage

in renal insufficiency

(creatinine clearance


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


vulgaris.

No antistaphylococcalor antipseudomonal

activity.

Children: 8 mg/kg/24

hr divided q 1224 hr

PO.

Adults: 400 mg/24 hr

divided q 1224 hr PO.

Probenecid.

Cefoperazone sodium

Cefobid.

Injection.

3rd generation

cephalosporin activeagainst many gram-

positive and gram-

negative pathogens.

Neonates: 100mg/kg/24 hr divided q

12 hr IV or IM.

Children: 100150


Adults: 24 g/24 hrdivided q 812 hr IV orIM (max dose: 12 g/24

hr).

Cautions: Highly protein

bound cephalosporinwith limited potencyreflected by weak

antipseudomonal

activity.

Variable gram-positive

activity. Primarily

hepatically eliminated in

bile.

Drug interaction:

Disulfiram-like reactionwith alcohol.

Cefotaxime sodium

Claforan.

Injection.

3rd generation


against gram-positive

and gram-negative

pathogens. No

antipseudomonal

activity.

Neonates: 7 days: 100

mg/kg/24 hr divided q12 hr IV or IM; >7

days:


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


>12,000 g: 150


8 hr IV or IM.


hr divided q 68 hr IV

or IM (meningitis: 200mg/kg/24 hr divided q

68 hr IV).


IV or IM (max: 12 g/24hr).

Cefotetan disodium

Cefotan.

Injection.

2nd generation


against S. aureus,

Streptococcus, H.


Kl ebsiell a, Proteus,

and Bacteroides.

Inactive against

Enterobacter.

Children: 4080

mg/kg/24 hr divided IVor IM q 12 hr.

Adults: 24 g/24 hr

divided q 12 hr IV orIM (max: 6 g/24 hr).

Cautions: Highly

protein-bound

cephalosporin, poor CNS

penetration; -Lactamsafety profile (rash,

eosinophilia), disulfiram-

like reaction withalcohol. Renally

eliminated

(20% in bile).

Cefoxitin sodium

Mefoxin.

Injection.

2nd generation


against S. aureus,

Streptococcus, H.


Kl ebsiell a, Proteus,and Bacteroides.

Inactive against

Enterobacter.


812 hr IV or IM.

Cautions: Poor CNS

penetration; -Lactam


eosinophilia). Renallyeliminated. Painful given

intramuscularly.



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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Children: 80160


68 hr IV or IM.


IV or IM (max dose: 12

g/24 hr).

Cefpodoxime proxetil

Vantin.

Tablet: 100 mg, 200 mg.


100 mg/5 mL.

3rd generation


against S. aureus,

Streptococcus, H.

infl uenzae, M .

catarrhali s, N.gonorr hoeae, E. coli,

Klebsiella, and

Proteus. No

antipseudomonal

activity.

Children: 10 mg/kg/24hr divided q 12 hr PO.

Adults: 200800 mg/24

hr divided q 12 hr PO

(max dose: 800 mg/24hr).

Uncomplicated

gonorrhea: 200 mg POas single-dose therapy.

Cautions:-Lactam

safety profile (rash,eosinophilia).

Renally eliminated. Does

not adequately penetrateCNS.

Increased bioavailability

when taken with food.

Drug interaction:

Probenecid;antacids and

H-2 receptor antagonistsmay decrease absorption.

Cefprozil

Cefzil.

Tablet: 250,500 mg.


250 mg/5 mL.

2nd generation


against S. aureus,

Streptococcus, H.

I nf luenzae, E. coli, M .

catarr hal is, Klebsiella,and Proteus.


hr divided q 812 hr

PO.

Adults: 5001,000

Cautions:-Lactam



eliminated. Goodbioavailability; food does

not affect bioavailability.



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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


mg/24 hr divided q 12

hr PO (max dose: 1.5

g/24 hr).

Ceftazidime

Fortaz, Ceptaz, Tazicer,

Tazidime.

Injection.

3rd generation



and gram-negative

pathogens including

Pseudomonas

aeruginosa.


7 days: 100 mg/kg/24hr divided q 12 hr IV or

IM;

>7 dyas 1,200 g: 100mg/kg/24 hr divided q

12 hr IV or IM; >1,200

g: 150 mg/kg/24 hrdivided q 8 hr IV or

IM.


hr divided q 8 hr IV orIM (meningitis: 150

mg/kg/24 hr IV divided

q 8 hr).


IV or IM (max: 812

g/24 hr).



eliminated. Increasing

pathogen resistance

developing with long-term, widespread use.

Drug interaction:

Probenecid.

Ceftiaoxime

Cefizox.

Injection.

3rd generation



and gram-negativepathogens. No

antipseudomonal

activity.

Children: 150 mg/kg/24hr divided q 68 hr IV

or IM.

Cautions:-Lactam

safety profile (rash,eosinophilia). Renally

eliminated.



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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF



IV or IM (max dose: 12

g/24 hr).

Ceftriaxone sodium

Rocephin.

Injection.

3rd generation



and gram-negative

pathogens. No

antipseudomonal

activity. Very potent

and-lactamase

stable.

Neonates: 5075 mg/kg

q 24 hr IV or IM.

Children: 5075 mg/kgq 24 hr IV or IM

(meningitis: 75 mg/kg

dose 1 then 80100mg/kg/24 hr divided q

1224 hr IV or IM).


IV or IM (max dose: 4g/24 hr).


eosinophilia).

Eliminated via kidney

(3365%) and bile; cancause sludging. Long

half-life and dose-

dependent protein

binding favors q 24 hrrather than q 12 hr

dosing. Can add 1%

lidocaine for IMinjection.

Cefuroxime (cefuroxime

axetil for oral

administration)

Ceftin, Kefurox, Zinacef.

Injection.

Suspension: 125 mg/5 mL.

Tablet: 125,250,500 mg.

2nd generation


against S. aureus,

Streptococcus, H.

infl uenzae, E. coli , M .

catarr hal is, Klebsiella,

and Proteus.

Neonates: 40100


Children: 200240


8 hr IV or IM;POadministration:

Cautions:-Lactam


eosinophilia).

Renally eliminated. Food

increases PO

bioavailability.

Drug interaction:

Probenecid.


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


2030 mg/kg/24 hr

divided q 8 hr PO.

Adults: 7501,500 mgq 8 hr IV or IM (max

dose: 6 g/24 hr).

Cephalexin

Keflex, Keftab.

Capsule: 250,500 mg

Tablet: 500 mg, 1 g.

Suspension: 125 mg/5 mL,250 mg/5 mL, 100 mg/mLdrops.

1st generation


against S. aureus,


Klebsiella, and

Proteus.

Children: 25100


68 hr PO.

Adults: 250500 mg q6 hr PO (max dose: 4

g/24 hr).

Cautions:-Lactam


eosinophilia). Renallyeliminated.

Drug interaction:

Probenecid.

Cephradine

Velosef

Capsule: 250,500 mg.Suspension: 125 mg/5 mL,

250 mg/5 mL.

1st generation


against S. aureus,

Streptococcus, E. coli ,Klebsiella, and

Proteus.

Children: 50100


612 hr PO.

Adults: 250500 mg q

612 hr PO (max dose:

4 g/24 hr).

Cautions:-Lactam


eliminated.Drug interaction:

Probenecid.

ChloramphenicolChloromycetin.

Injection.

Capsule: 250 mg.

Ophthalmic, otic solutions.

Broad-spectrumprotein sythesis

inhibitor active

against many gram-

positive and gram-

negative bacteria,

Salmonella,

vancomycin-

Cautions: Gray-babysyndrome (from too-highdose in neonate), bone

marrow suppression

aplastic anemia (monitorhematocrit, free serum

iron).


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DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Ointment. anaerobes, resistantEnterococcus faecium,

Bacteroides, other

Mycoplasma,

Chlamydia, and

Rickettsia;

Pseudomonasusually

resistant.

Neonates: Initial

loading dose 20 mg/kg

followed 12 hr later by:postnatal age 7 days:

25 mg/kg/24 hr q 24 hr

IV; >7 days: 2,000 g:25 mg/kg/24 hr q 24 hr

IV; >2,000 g: 50


12 hr IV.

Children: 5075


68 hr IV or PO(meningitis: 75100

mg/kg/24 hr IV dividedq 6 hr).

Adults: 50 mg/kg/24 hr

divided q 6 hr IV or PO

(max dose: 4 g/24 hr).

Drug interactions:

Phenytoin, phenobarbital,

rifampin may decreaselevels.

Target serum

concentrations: Peak 2030 mg/L;trough 510

mg/L.

Ciprofloxacin

Cipro.

Tablet: 100,250,500,750

mg.

Injection.

Ophthalmic solution and

ointment.

Otic suspension.

Oral suspension: 250 and

Quinolone antibiotic

active against P.

aeruginosa, Serr atia,

Enterobacter, Shigell a,

Salmonella,

Campylobacter,Neisseria gonorrhoeae,

H . inf luenzae, M.

catarrhalis, some S.

aureus, and

Streptococcus.

Neonates: 10 mg/kg q

Cautions: Concerns of

joint destruction injuvenile animals not seen

in humans; tendonitis,

superinfection, dizziness,

confusion, crystalluria,some photosensitivity.

Drug interactions:

Theophylline,magnesium-, aluminum-,

or calcium-containing

antacids, sucralfate,


20/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


500 mg/5 mL. 12 hr PO or IV.

Children: 1530mg/kg/24 hr divided q12 hr PO or IV;cystic

fibrosis: 2040

mg/kg/24 hr divided q812 hr PO or IV.

Adults: 250750 mg q

12 hr; 200400 mg IV

q 12 hr PO (max dose:1.5 g/24 hr).

probenecid, warfarin,

cyclosporine.

Clarithromycin

Biaxin.

Tablet: 250,500 mg.


250 mg/5 mL.

Macrolide antibiotic

with activity against

S. aur eus,

Streptococcus, H.

in f luenzae, Legionella,

Mycoplasma, and C.

trachomatis.


hr divided q 12 hr PO.

Adults: 250500 mg q

12 hr PO (max dose: 1g/24 hr).

Cautions: Adverse

events less than

erythromycin;

gastrointestinal upset,dyspepsia, nausea,

cramping.

Drug interactions: Sameas erythromycin:

astemizole

carbamazepine,

terfenadine cyclosporine,theophylline, digoxin,

tacrolimus.

Clindamycin

Cleocin.

Capsule: 75,150,300 mg.


Injection.

Topical solution, lotion,and gel.

Vaginal cream.

Protein synthesis

inhibitor active

against most gram-

positive aerobic and

anaerobic cocci except

Enterococcus.


7 days 2,000 g: 15 mg/kg/24

hr divided q 8 hr IV orIM; >7 days


21/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


IM divided q 12 hr;

1,2002,000 g: 15

mg/kg/24 hr divided q8 hr IV or IM; >2,000

g: 20 mg/kg/24 hr

divided q 8 hr IV or

IM.

Children: 1040


68 hr IV, IM, or PO.

Adults: 150600 mg q

68 hr IV, IM, or PO

(max dose: 5 g/24 hr IVor IM or 2 g/24 hr PO).

Cloxacillin sodium

Tegopen.



Penicillinase-resistant

penicillin active

against S. aureusand

other gram-positive

cocci except

Enterococcusand

coagulase-negative

staphylococci.

Children: 50100


6 hr PO.

Adults: 250500 mg q

6 hr PO (max dose: 4

g/24 hr).


eosinophilia).

Primarily hepaticallyeliminated; requires dose

reduction in renal

disease. Food decreases

bioavailabilty.Drug interaction:

Probenecid.

Co-trimoxazole

(trimethoprim-

sulfamethoxazole; TMP-

SMZ)

Bactrim, Cotrim, Septra,Sulfatrim.

Tablet: SMZ 400 mg and

TMP 80 mg.

Tablet DS: SMZ 800 mg

Antibiotic

combination with

sequential antagonism

of bacterial folatesynthesis with broad

antibacterial activity:

Shigell a, Legionella,

Nocardia, Chlamydia,

Pneumocystis car in ii .

Dosage based on TMP

Cautions: Drug dosed on

TMP (trimethoprim)component.

Sulfonamide skin

reactions: rash, erythemamultiforme, Stevens-

Johnson syndrome,

nausea, leukopenia.Renal and hepatic

elimination; reduce dose


22/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


and TMP 160 mg.

Suspension: SMZ 200 mgand TMP 40 mg/5 mL.

Injection.

component.

Children: 620 mgTMP/kg/24 hr or IV

divided q 12 hr PO.

P. carinii pneumonia:

1520 mg TMP/kg/24

hr divided q 12 hr POor IV.

P. carinii prophylaxis:

5 mg TMP/kg/24 hr or

3 times/wk PO.

Adults: 160 mg TMP q12 hr PO.

in renal failure.

Drug interactions:Protein displacementwith warfarin, possibly

phenytoin, cyclosporine.

Demeclocycline

Declomycin.

Tablet: 150,300 mg.

Capsule: 150 mg.

Tetracycline active

against most gram-

positive cocci except

Enterococcus, many

gram-negative bacilli,

anaerobes, Borrelia

burgdorferi(Lyme

disease), Mycoplasma,

and Chlamydia.

Children: 812


612 hr PO.

Adults: 150 mg PO q

68 hr.

Syndrome ofinappropriate

antidiuretic hormone

secretion: 9001,200mg/24 hr or 1315mg/kg/24 hr divided q

68 hr PO with dose

reduction based on

response to 600900mg/24 hr.

Cautions: Teeth staining,

possibly permanent (ifadministered


23/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Dicloxacillin

Dynapen, Pathocil.

Capsule: 125,250,500 mg.

Suspension: 62.5 mg/5

mL.


penicillin activeagainst S. aureusand

other gram-positive

cocci except

Enterococcusand

coagulase-negative

staphylococci.

Children: 12.5100


6 hr PO.

Adults: 125500 mg q

6 hr PO.


eosinophilia).

Primarily renally (65%)and bile (30%)

elimination. Food may

decrease bioavailability.

Drug interaction:

Probenecid.

Doxycycline

Vibramycin, Doxy.

Injection.

Capsule: 50,100 mg.

Tablet: 50,100 mg.


Syrup: 50 mg/5 mL.

Tetracycline antibiotic

active against most

gram-positive cocci

except

Enterococcus, many

gram-negative bacilli,

anaerobes, Borrelia

burgdorferi(Lyme

disease), Mycoplasma,and Chlamydia.


hr divided q 1224 hrPO or IV (max dose:

200 mg/24 hr).

Adults: 100200 mg/24

hr divided q 1224 hrPO or IV.

Cautions: Teeth staining,

possibly permanent (


24/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


mg.

Suspension:estolate 125mg/5 mL, 250 mg/5 mL,EES 200 mg/5 mL, 400

mg/5 mL.

Estolate drops: 100mg/mL.

EES drops: 100 mg/2.5

mL.

Available in combinationwith sulfisoxazole

(Pediazole), dosed onerythromycin content.

pneumoniae. May also

be used to promotegastrointestinal

motility and improve

feeding intolerance in

preterm infants.

Neonates: Postnatal age7 days: 20 mg/kg/24

hr divided q 12 hr PO;

>7 days


25/51


26/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


positive cocci and

gram-negative bacilliincluding P.

aeruginosaand

anerobes. No activity

against

Stenotrophomonas

maltophilia.


7 days 1,200 g: 40 mg/kg

divided q 12 hr IV orIM;postnatal age >7

days 1,2002,000 g: 40mg/kg q 12 hr IV or

IM; >2,000 g: 60 mg/kg

q 8 hr IV or IM.

Children: 60100


68 hr IV or IM.

Adults: 24 g/24 hr

divided q 68 hr IV orIM (max dose: 4 g/24hr).

possesses no antibacterialactivity; reduces renal

imipenem metabolism.

Primarily renallyeliminated.

Drug interaction:

Possibly ganciclovir.

Linezolid

Zyvox.

Tablet: 400, 600 mg.

Oral suspension: 100 mg/5

mL.

Injection: 100 mg/5 mL.

Oxazolidinone

antibiotic active


cocci (especially drug-

resistant organisms),

including

Staphylococcus,

Streptococcus,Enterococcus faecium,

and E. f ecalis.

Interferes with

protein synthesis by

binding to 50S

ribosome subunit.

Adverse events:Myelosuppression,

pseudomembranous

colitis, nausea, diarrhea,headache.

Drug interaction:

Probenecid.


27/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Children: 10 mg/kg q

12 hr IV or PO.

Adults: Pneumonia:600 mg q 12 hr IV or

PO;skin infections: 400

mg q 12 hr IV or PO.

Loracarbef

Lorabid.

Capsule: 200 mg.


200 mg/5 mL.

Carbacephem very

closely related to

cefaclor (2nd

generation

cephalosporin) active

against S. aureus,Streptococcus, H.

infl uenzae, M .

catarrhali s, E. coli,

Klebsiella, and

Proteus.

Children: 30 mg/kg/24hr divided q 12 hr PO

(max dose: 2 g).

Adults: 200400 mg q

12 hr PO (max dose:800 mg/24 hr).

Cautions:-Lactam


eliminated.


Meropenem

Merrem.

Injection.

Carbapenem

antibiotic active

against broad-

spectrum gram-

positive cocci and

gram-negative bacilli

including P.

aeruginosaand

anerobes. No activityagainst

Stenotrophomonas

maltophilia.


hr divided q 8 hr IVmeningitis: 120

Cautions:-Lactam

safety profile; appears to

possess less

CNS excitation than

imipenem. 80% renal

elimination.

Drug interaction:

Probenecid.


28/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


mg/kg/24 hr [max: 6

g/24 hr] q 8 hr IV.

Adults: 1.53 g q 8 hrIV.

Metronidazole

Flagyl, Metro-IV, generic.

Topical gel, vaginal gel.

Injection.

Tablet: 250,500 mg.

Highly effective in the

treatment of

infections due to

anaerobes.

Neonates:


29/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


7 days: 150 mg/kg/24

hr divided q 12 hr IV;

>7 days: 225 mg/kgdivided q 8 hr IV.

Children: 200300

mg/kg/24 hr divided q46 hr IV;cystic

fibrosis 300450

mg/kg/24 hr IV.

Adults: 24 g/dose q 46 hr IV (max dose: 12

g/24 hr).

liver function test results.

Renally eliminated.

Inactivated by -lactamase enzyme.

Drug interaction:

Probenecid.

Mupirocin

Bactroban.

Ointment.

Topical antibiotic

active against

Staphylococcusand

Streptococcus.

Topical application:

Nasal (eliminate nasalcarriage) and to the

skin 24 times per day.

Caution: Minimal systemic

absorption as drug metabolizedwithin the skin.

Nafcillin sodiumNafcil, Unipen.

Injection.

Capsule: 250 mg.

Tablet: 500 mg.

Penicillinase-resistantpenicillin active

against S. aureusand

other gram-positive

cocci except

Enterococcusand

coagulase-negative

staphylococci.


7 days 1,2002,000 g:50 mg/kg/24 hr divided

q 12 hr IV or IM;>2,000 g: 75 mg/kg/24hr divided q 8 hr IV or

IM;postnatal age >7

days 1,2002,000 g: 75

mg/kg/q 8 hr; >2,000 g:100 mg/kg divided q 6

Cautions:-Lactamsafety profile (rash,eosinophilia), phlebitis;painful given

intramuscularly; oral

absorption highlyvariable and erratic (not

recommended).

Adverse effect:

Neutropenia.


30/51

DRUG (TRADE NAMES,

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INDICATIONS

(MECHANISM OF


8 hr IV (meningitis:

200 mg/kg/24 hr

divided q 6 hr IV).

Children: 100200


46 hr IV.

Adults: 412 g/24 hr

divided q 46 hr IV


Nalidixic acid

NegGram.Tablet: 250,500,1,000 mg.


1st generation

quinolone effective for

short-term treatment

of lower urinary tract

infections caused by

E. coli , Enterobacter ,

Klebsiella, and

Proteus.


6 hr PO;suppressive

therapy 2533

mg/kg/24 hr divided q68 hr PO.

Adults: 1 g q 6 hr

PO;suppressivetherapy: 500 mg q 6 hr

PO.

Cautions: Vertigo,

dizziness, rash. Not foruse in systemic

infections.

Drug interactions:

Liquid antacids.

Neomycin sulfate

Mycifradin, generic.

Tablet: 500 mg.

Topical cream, ointment.

Solution: 125 mg/5 mL.

Aminoglycoside

antibiotic used for

topical application or

orally before surgery

to decreasegastrointestinal flora

(nonabsorbable) and

hyperammonemia.

Infants: 50 mg/kg/24 hrdivided q 6 hr PO.

Cautions: In patients

with renal dysfunction

because small amountabsorbed may

accumulate.

Adverse events:Primarily related to

topical application,

abdominal cramps,diarrhea, rash.

Aminoglycoside


31/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Children: 50100


68 hr PO.

Adults: 5002,000

mg/dose q 68 hr PO.

ototoxicity and

nephrotoxicity if

absorbed.

Nitrofurantoin

Furadantin, Furan,

Macrodantin.

Capsule: 50,100 mg.

Extended-release capsule:

100 mg.

Macrocrystal: 50,100 mg.


Effective in the

treatment of lower

urinary tract

infections caused by

gram-positive and

gram-negative

pathogens.


hr divided q 6 hr PO

(max dose: 400 mg/24hr); suppressive therapy

12.5 mg/kg/24 hr

divided q 1224 hr PO(max dose: 100 mg/24

hr).

Adults: 50100 mg/24

hr divided q 6 hr PO.

Cautions: Vertigo,

dizziness, rash, jaundice,

interstitial pneumonitis.

Do not use with

moderate to severe renal

dysfunction.

Drug interactions:

Liquid antacids.

Ofloxacin

Ocuflox 0.3% ophthalmic

solution: 1,5,10 mL.

Floxin 0.3% otic solution:5,10 mL.

Quinolone antibiotic

for treatment of

conjunctivitis or

corneal ulcers

(ophthalmic solution);

and otitis externa and

chronic suppurative

otitis media (otic

solution) caused by

susceptible gram-positive, gram-

negative, anaerobic

bacteria, or

Chlamydia

trachomatis.

Child >112 yr:

Adverse events: Burning,

stinging, eye redness

(ophthalmic solution),dizziness with otic solution if

not warmed.


32/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Conjunctivitis: 12

drops in affected eye(s)

q 24 hr for 2 days,then 12 drops qid for 5

days.

Corneal ulcers: 12drops q 30 min while

awake and at 4 hours at

night for 2 days, then

12 drops hourly for 5days while awake, then

12 drops q 6 hr for 2

days.Otitis externa (otic

solution):5 drops into

affected ear bid for 10

days.

Chronic suppurative

otitis media: treat for

14 days.

Child >12 yr and

adults:

Ophthalmic solutiondoses same as for

younger children.

Otitis externa (oticsolution): Use 10 drops

bid for 10 or 14 days as

for younger children.

Oxacillin sodium

Prostaphlin.

Injection.




penicillin active

against S. aureusandother gram-positive

cocci except

Enterococcusand

coagulase-negative

staphylococci.


Cautions:-Lactam


eosinophilia).

Moderate oral

bioavailability (3565%).

Primarily renallyeliminated.

Drug interaction:


33/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


7 days 1,2002,000 g:

50 mg/kg/24 hr divided

q 12 hr IV; >2,000 g:75 mg/kg/24 hr IV

divided q 8 hr

IV;postnatal age >7

days 2,000 g: 100

mg/kg/24 hr IV divided

q 6 hr IV.

Infants: 100200


46 hr IV.

Children: PO 50100


46 hr IV.

Adults: 212 g/24 hr

divided q 46 hr IV


Probenecid.

Adverse effect:Neutropenia.

Penicillin G

Injection.

Tablets.

Penicillin active

against most gram-

positive cocci; S.

pneumoniae

(resistance is

increasing), group A

streptococcus, and

some gram-negative

bacteria (e.g., N.

gonorr hoeae, N.meningitidis).


7 days 1,2002,000 g:

50,000 units/kg/24 hr


IM (meningitis:

Cautions:-Lactam

safety profile (rash,eosinophilia), allergy,

seizures with excessive

doses particularly inpatients with marked

renal disease. Substantial

pathogen resistance.

Primarily renally

eliminated.

Drug interaction:

Probenecid.


34/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF




IM); >2,000 g: 75,000units/kg/24 hr divided q

8 hr IV or IM

(meningitis: 150,000

units/kg/24 hr divided q8 hr IV or IM);

postnatal age >7 days

1,200 g: 50,000

units/kg/24 hr divided q12 hr IV (meningitis:


divided q 12 hrIV);1,2002,000 g:

75,000 units/kg/24 hr q

8 hr IV (meningitis:225,000 units/kg/24 hr

divided q 8 hr IV);

>2,000 g: 100,000

units/kg/24 hr divided q6 hr IV (meningitis:


divided q 6 hr IV).

Children: 100,000



IM (max: 400,000units/kg/24 hr).

Adults: 224 millionunits/24 hr divided q 46 hr IV or IM

Penicillin G, benzathine

Bicillin.

Injection.

Long-acting

repository form ofpenicillin effective in

the treatment of

infections responsive

to persistent, low

penicillin

concentrations (14

Cautions:-Lactam

safety profile (rash,eosinophilia), allergy.

Administer by IMinjection only.

Substantial pathogen

resistance. Primarilyrenally eliminated.


35/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


wk), e.g., group A

streptococcuspharyngitis,

rheumatic fever

prophylaxis.

Neonates >1,200 g:

50,000 units/kg IMonce.

Children: 300,0001.2

million units/kg q 34

wk IM (max: 1.22.4million units/dose).

Adults: 1.2 million

units IM q 34 wk.

Drug interaction:

Probenecid.

Penicillin G, procaine

Crysticillin.

Injection.

Repository form of

penicillin providing

low penicillin

concentrations for 12

hr.

Neonates >1,200 g:


IM.

Children: 25,000


IM for 10 days (max:4.8 million units/dose).

Gonorrhea: 100,000

units/kg (max: 4.8million units/24 hr) IM

once with probenecid

25 mg/kg (max dose: 1

g)

Adults: 0.64.8 million

units q 1224 hr IM.

Cautions:-Lactam

safety profile (rash,eosinophilia) allergy.

Administer by IM

injection only.Substantial pathogen

resistance. Primarily

renally eliminated.Drug interaction:

Probenecid.

Penicillin V

Pen VK, V-Cillin K.

Preferred oral dosing

form of penicillin,

active against most

Cautions:-Lactam


eosinophilia), allergy,


36/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Tablet: 125,250,500 mg.

Suspension: 125 mg/5 mL,250 mg/5 mL.

gram-positive cocci; S.

pneumoniae(resistance is

increasing), other

Streptococcus, and

some gram-negative

bacteria (e.g., N.

gonorr hoeae, N.

meningitidis).

Children: 2550


Adults: 125500 mg q

68 hr PO (max dose: 3g/24 hr).

seizures with excessivedoses particularly in

patients with renal

disease. Substantialpathogen resistance.

Primarily renally

eliminated. Inactivated

by penicillinase.

Drug

interaction:Probenecid.

Piperacillin

Pipracil.

Injection.

Extended-spectrum

penicillin active

against E. coli ,


P. aeruginosa, and

Bacteroides.

Neonates: Postnatal age7 days 150 mg/kg/24hr divided q 812 hr

IV; >7 days; 200 mg/kg

divided q 68 hr IV.

Children: 200300


46 hr IV;cysticfibrosis: 350500

mg/kg/24 hr IV.

Adults: 24 g/dose q 46 hr (max dose: 24 g/24hr) IV.

Cautions: -Lactamsafety profile (rash,

eosinophilia); painful

given intramuscularly;each gram contains 1.9

mEq sodium. Interferes

with platelet

aggregation/serumsicknesslike reaction

with high doses;

increases in liverfunction tests.

Renally eliminated.

Inactivated bypenicillinase.

Drug interaction:

Probenecid.

Piperacillin-tazobactam

Zosyn.

Injection.

Extended-spectrum

penicillin

(piperacillin)

combined with a-

Cautions:-Lactam


eosinophilia); painfulgiven intramuscularly;


37/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


lactamase inhibitor

(tazobactam) activeagainst S. aureus, H.



Acinetobacter, P.

aeruginosa, and

Bacteroides.

Children: 300400


68 hr IV or IM.

Adults: 3.375 g q 68

hr IV or IM.

each gram contains 1.9mEq sodium. Interferes

with platelet aggregation,

serum sincknesslikereaction with high doses,

increases in liver

function test results.

Renally eliminated.

Drug interaction:

Probenecid.

Quinupristin/dalfopristin

Synercid.

IV injection: powder for

reconstitution, 10 mL

contains

150 mg quinupristin, 350mg dalfopristin.

Streptogramin

antibiotic

(quinupristin) active

against vancomycin-

resistant E. faecium

(VRE) and

methicillin-resistant S.

aureus. Not active

against E. faecali s.

Children and adults:VRE:7.5 mg/kg q 8 hr

IV for VRE;skin

infections: 7.5 mg/kg q12 hr IV.

Adverse events: Pain,

edema, or phlebitis at

injection site, nausea,diarrhea.

Drug interactions:

Synercid is a potentinhibitor of CYP3A4.

Sulfadiazine

Tablet: 500 mg.

Sulfonamide

antibiotic primarily

indicated for the

treatment of lower

urinary tractinfections due to E.

coli , P. mirabil is, and

Klebsiella.

Toxoplasmosis:


Cautions: Rash, Stevens-

Johnson syndrome,

nausea, leukopenia,

crystalluria. Renal and

hepatic elimination;avoid use with renal

disease. Half-life 10 hr.

Drug interactions:

Protein displacement

with warfarin, phenytoin,methotrexate.


38/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


12 hr PO with

pyrimethamine 1

mg/kg/24 hr PO (withfolinic acid).

Children: 120200

mg/kg/24 hr divided q6 hr PO with

pyrimethamine 2


12 hr PO 3 days then1 mg/kg/24 hr (max

dose: 25 mg/24 hr) with

folinic acid.Rheumatic fever

prophylaxis: 30 kg:

500 mg/24 hr q 24 hr

PO; >30 kg: 1 g/24 hr q24 hr PO.

Sulfamethoxazole

Gantanol.

Tablet: 500 mg.


Sulfonamide

antibiotic used for the

treatment of otitis

media, chronic

bronchitis, and lowerurinary tract

infections due to

susceptible bacteria.

Children: 5060


Adults: 1 g/dose q 12 hr

PO (max dose: 3 g/24

hr).

Cautions: Rash, Stevens-

Johnson syndrome,

nausea, leukopenia,



disease. Half-life 12 hr.Initial dose often a

loading dose (doubled).

Drug interactions:Protein displacement

with warfarin, phenytoin,

methotrexate.

Sulfisoxazole

Gantrisin.

Tablet: 500 mg.


Sulfonamide

antibiotic used for the

treatment of otitis

media, chronic

bronchitis, and lower

urinary tract

Cautions: Rash, Stevens-Johnson syndrome,

nausea, leukopenia,




39/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Ophthalmic solution,

ointment.infections due to

susceptible bacteria.Children: 120150

mg/kg/24 hr divided q46 hr PO (max dose: 6

g/24 hr).

Adults: 48 g/24 hrdivided q 46 hr PO.

disease. Half-life 712

hr. Initial dose often aloading dose (doubled).

Drug interactions:

Protein displacement

with warfarin, phenytoin,methotrexate.

Ticarcillin

Ticar.

Injection.

Extended-spectrum

penicillin active

against E. coli ,


P. aeruginosa, and

Bacteroides.


7 days 7 days:

7 days 2,000 g: 300mg/kg/24 hr divided q

68 hr IV.


46 hr IV;cystic

fibrosis: 400600

mg/kg/24 hr IV.

Adults: 24 g/dose q 4

6 hr IV (max dose: 24

g/24 hr).


eosinophilia); painful

given intramuscularly;each gram contains 56

mEq sodium. Interferes

with platelet aggregation;

increases in liverfunction tests. Renally

eliminated. Inactivated

by penicillinase.

Drug interaction:

Probenecid.

Ticarcillin-clavulanate Extended-spectrum

penicillin (ticarcillin)



40/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Timentin.

Injection.

combined with a-

lactamase inhibitor(clavulanate) active

against S. aureus, H.

influenzae,

Enterobacter, E. coli ,

Serrati a, P.

aeruginosa,

Acinetobacter, and

Bacteroides.

Children: 280400mg/kg/24 hr q 48 hr

IV or IM.

Adults: 3.1 g q 48 hrIV or IM (max dose:

1824 g/24 hr).

eosinophilia); painfulgiven intramuscularly;

each gram contains 56

mEq sodium. Interfereswith platelet aggregation;

increases in liver

function tests. Renally

eliminated.

Drug interaction:

Probenecid.

Tobramycin

Nebcin, Tobrex.

Injection.

Ophthalmic solution,

ointment.

Aminoglycoside

antibiotic active


bacilli, especially E.

coli, Klebsiella,


Proteus, and

Pseudomonas.


7 days, 1,2002,000 g:2.5 mg/kg q 1218 hr

IV or IM; >2,000 g: 2.5

mg/kg q 12 hr IV orIM;postnatal age >7

days, 1,2002,000 g:

2.5 mg/kg q 812 hr IV

or IM; >2,000 g: 2.5mg/kg q 8 hr IV or IM.

Children: 2.5 mg/kg/24

hr divided q 812 hr IVor IM. Alternatively

may administer 57.5

mg/kg/24 hr IV.

Cautions: S.

pneumoniae, other

Streptococcus, andanaerobes are resistant.

May cause ototoxicity

and nephrotoxicity.

Monitor renal function.Drug eliminated renally.

Administered IV over

3060 min.

Drug interactions: May

potentiate other ototoxic

and nephrotoxic drugs.

Target serum

concentrations: Peak 6

12 mg/L;trough


41/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


Preservative-free

preparation for

intraventricular orintrathecal use:neonate:

1 mg/24 hr; children:

12 mg/24 hr; adults:

48 mg/24 hr.

Adults: 36 mg/kg/24

hr divided q 8 hr IV or

IM.

Trimethoprim

Proloprim, Trimpex.

Tablet: 100,200 mg

Folic acid antagonist

effective in theprophylaxis and

treatment ofE. coli ,

Kl ebsiella, Proteus

mirabilis, and

Enterobacterurinary

tract infections; P.

cariniipneumonia.

Children: For urinary

tract infection: 46


12 hr PO.

Children >12 yr and

adults: 100200 mg q12 hr PO.

P. carinii pneumonia

(with dapsone):1520mg/kg/24 hr divided q

6 hr for 21 days PO.

Cautions: Megaloblastic

anemia, bone marrowsuppression, nausea,

epigastric distress, rash.

Durg interactions:Possible interactions with

phenytoin, cyclosporine,

rifampin, warfarin.

Vancomycin

Vancocin, Luphocin.

Injection.

Capsule: 125 mg, 250 mg.

Suspension.

Glycopeptide

antibiotic activeagainst most gram-

positive pathogens

including

Staphylococcus

(including methicillin-

resistant S. aureus

Cautions: Ototoxicity

and nephrotoxicityparticularly when co-administered with other

ototoxic and nephrotoxic

drugs. Infuse IV over 45

60 min. Flushing (red-man syndrome)


42/51

DRUG (TRADE NAMES,

FORMULATIONS)

INDICATIONS

(MECHANISM OF


and coagulase-

negativestaphylococci), S.

pneumoniaeincluding

penicillin-resistant

strains, Enterococcus

(resistance is

increasing), and

Clostridium diffi cile-

associated colitis.

Neonates: Postnatal age7 days, 2,000 g: 30 mg/kg/24

hr divided q 12 hrIV;postnatal age >7

days, 2,000 g: 45 mg/kg/24hr divided q 8 hr IV.

Children: 4560

mg/kg/24 hr divided q812 hr IV;

Clostridium difficile-

associated colitis; 4050 mg/kg/24 hr divided

q 68 hr PO.

Adults: 0.51 g IV q 12hr IV.

associated with rapid IVinfusions, fever, chills,

phlebitis (central line is

preferred). Renallyeliminated.

Target serum

concentrations: Peak (1hr after 1 hr infusion)

3040 mg/L;trough 510

mg/L.

Penicillins remain the drugs of choice for many common pediatric infections caused by group Aand group B streptococcus, Treponema pallidum (syphilis),Listeria monocytogenes, and

Neisseria meningitidis. The semisynthetic penicillins (nafcillin, cloxacillin, dicloxacillin) are


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useful for management of susceptible staphylococcal infections, although increasing incidence of

MRSA has limited the usefulness of these drugs. The aminopenicillins (ampicillin, amoxicillin)

were developed to provide broad-spectrum activity against gram-negative organisms, including

E. coli andH. influenzae, but the emergence of resistance has limited their utility in many

clinical settings. The carboxypenicillins (carbenicillin, ticarcillin) and ureidopenicillins

(piperacillin, mezlocillin, azlocillin) also have bactericidal activity against most strains ofP.aeruginosa.

Resistance to penicillin is mediated by a variety of mechanisms (see Table 179-1 ). Theproduction of -lactamase is a common mechanism exhibited by many organisms that may be

overcome, with variable success, by including a -lactamase inhibitor with the penicillin. These

combination products (ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam)

are very useful for management of resistant isolates if the resistance is -lactamase mediated.Notably, S. aureus and S. pneumoniaemediate -lactam resistance through mechanisms other

than -lactamase production, rendering these combination agents of little value for the

management of these infections.

Adverse reactions to penicillins are noted in Table 179-4 .

TABLE 179-4 -- Adverse Reactions to Penicillins[*]

TYPE OF REACTION

FREQUENCY

(%)

OCCURS MOST FREQUENTLY

WITH[*]

ALLERGIC

IgE antibody 0.0040.4 Penicillin G

Anaphylaxis

Early urticaria (


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TYPE OF REACTION

FREQUENCY

(%)

OCCURS MOST FREQUENTLY

WITH[*]

Enterocolitis


45/51


46/51

Adverse reactions to cephalosporins are noted in Table 179-6 .

TABLE 179-6 -- Potential Adverse Effects of Cephalosporins

TYPE SPECIFIC FREQUENCY

Hypersensitivity Rash 13%

Urticaria


47/51

TYPE SPECIFIC FREQUENCY

Phlebitis Rare

From Mandell GL, Bennett JE, Dolin R (editors):Principles and Practice of Infectious Diseases,

6th ed, Vol 1. Philadelphia, Elsevier, 2005, p 303.

Ceftriaxone. Cephalosporins with thiomethyl tetrazole ring (MTT) side chain.

Carbapenems.

The carbapenems include imipenem, which is a combination of thienamycin and cilastatin, andthe newer agents, meropenem and ertapenem. The basic structure of these agents is similar to

that of -lactam antibiotics, with a similar mechanism of action. The carbapenems provide the

broadest spectrum of antibacterial activity of any licensed class of antibiotics, and are active

against gram-positive, gram-negative, and anaerobic organisms. Meropenem is licensed fortreatment of pediatric meningitis. MRSA andEnterococcus faecium are not susceptible to

carbapenems. Carbapenems also tend to be poorly active against Stenotrophomonas maltophilia,

rendering their use for cystic fibrosis patients colonized with this organism problematic. The 1stcarbapenem approved for clinical use was imipenem-cilastatin, which has a propensity to cause

seizures in children, particularly in the setting of meningitis, and therefore meropenem is more

suitable for pediatric use.

Glycopeptides.

Glycopeptide antibiotics include vancomycin and teicoplanin, the less commonly availableanalog. These agents are bacteriocidal and act via inhibition of cell wall biosynthesis. Theantimicrobial activity of the glycopeptides is limited to gram-positive organisms, including S.

aureus, coagulase-negative staphylococci, pneumococcus,Enterococcus, Bacillus, and

Corynebacterium. Vancomycin is frequently employed in pediatric practice and is of particularvalue for serious infections, including meningitis, caused by MRSA and penicillin- and

cephalosporin-resistant S. pneumoniae. Vancomycin is also commonly used for infections in the

setting of fever and neutropenia, in combination with other antibiotics, in oncology patients (seeChapter 177 ), and infections associated with indwelling medical devices (see Chapter 178 ).

Oral formulations of vancomycin are occasionally used to treat pseudomembranous colitis due to

Clostridium difficile infections; intrathecal therapy may also be used for selected CNS infections.

Vancomycin must be administered with care due to its propensity to produce red-man syndrome,which is a reversible adverse effect that is rare in young children and can typically be readily

managed by slowing the rate of infusion of the drug.

Aminoglycosides.

Aminoglycoside antibiotics include streptomycin, kanamycin, gentamicin, tobramycin,

netilmicin, and amikacin. The most commonly used aminoglycosides in pediatric practice aregentamicin and tobramycin. They exert their mechanism of action via inhibition of bacterial

protein synthesis. Although they are most commonly used to treat gram-negative infections, the

aminoglycosides are broad-spectrum agents and have activity against S. aureus and provide


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synergistic activity against group B streptococcus,L. monocytogenes, viridans streptococci,

corynebacteria JK,Pseudomonas, Staphylococcus epidermidis, andEnterococcus when co-

administered with a -lactam agent. Aminoglycoside use has decreased with the development ofnewer alternatives, but they still play a key role in pediatric practice in the management of

neonatal sepsis, urinary tract infections, gram-negative sepsis, and complicated intra-abdominal

infections; infections in cystic fibrosis patients (including both parenteral and aerosolized formsof therapy); and in oncology patients with fever and neutropenia. Aminoglycosides, in particularstreptomycin, are also important in the management ofFrancisella tularensis, Mycobacterium

tuberculosis, and atypical mycobacterial infections. Toxicities of aminoglycoside therapy include

nephrotoxicity and ototoxicity (cochlear and/or vestibular), and serum levels as well as renalfunction and hearing should be monitored for patients on long-term therapy. Toxicities of

aminoglycosides may be reduced by the use of once-daily dosing regimens based on monitoring

serum levels. Hypokalemia, volume depletion, hypomagnesemia, and other nephrotoxic drugs

may increase the renal toxicity of aminoglycosides. A rare complication of aminoglycosides isneuromuscular blockade, which may occur in the presence of other neuromuscular blocking

agents and with infant botulism.

Tetracyclines.

The tetracyclines (tetracycline hydrochloride, doxycycline, and minocycline) are bacteriostaticantibiotics that exhibit their antimicrobial effect by binding to the bacterial 30S ribosomalsubunit, inhibiting protein translation. These agents have a broad spectrum of antimicrobial

activity against gram-positive and -negative bacteria, rickettsia, and some parasites. The oral

bioavailability of these agents facilitates this route of dosing for many infections including

Rocky Mountain spotted fever, ehrlichiosis, Lyme disease, and malaria. Tetracyclines must beprescribed judiciously to children


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antibiotics developed for clinical use, relatively few remain available for pediatric practice. The

most important agent is the combination of trimethoprim-sulfamethoxazole, which is commonly

used for treatment of urinary tract infections and forPneumocystis carinii infections inimmunocompromised patients. Other commonly used sulfonamides include sulfisoxazole, which

is used to treat urinary tract infections, and sulfadiazine, which is used to treat toxoplasmosis and

as alternative prophylaxis against acute rheumatic fever.

Macrolides.

The macrolide antibiotics most commonly employed in pediatric practice include erythromycinand the newer agents clarithromycin and azithromycin. These agents bind to the 50S subunit ofthe bacterial ribosome and block elongation of bacterial polypeptides. The spectrum of antibiotic

activity includes many gram-positive infections, including S. aureus and group A streptococcus,

although resistance to these agents is now fairly widespread, limiting the usefulness of

macrolides for skin and soft tissue infections and streptococcal pharyngitis. The newermacrolides, azithromycin and clarithromycin, have demonstrated efficacy for otitis media. All of

the members of this class have an important role in the management of pediatric respiratoryinfections, including atypical pneumonia caused byM. pneumoniae, Chlamydia pneumoniae, andLegionella pneumophila, as well as infections caused byBordetella pertussis.

Telithromycin is a ketolide antibiotic derived from the macrolide erythromycin. It is FDAapproved in adults for the treatment of mild to moderate community-acquired pneumonia, acute

exacerbations of chronic bronchitis, and acute sinusitis, having good activity against the agents

causing these infections (pneumococcus,M. pneumoniae, C. pneumoniae, andL. pneumophilafor community-acquired pneumonia;M. catarrhalis andH. influenzae for sinusitis).

Drug interactions are common with erythromycin and telithromycin, and less so withclarithromycin. These agents can inhibit the CYP3A4 enzyme system, resulting in increased

levels of certain drugs such as astemizole, cisapride, the statins, pimozide, and theophylline.

Other agents (itraconazole) may increase macrolide levels, while rifampin, carbamazepine, andphenytoin may decrease macrolide levels. There are few reported adverse drug interactions with

azithromycin. Cross-resistance may develop between a macrolide and the subsequent use of

clindamycin.

Lincosamides.

The prototype of the lincosamide class of antibiotics is clindamycin, which acts at the ribosomal

level to exert its antimicrobial effect. The spectrum of activity includes gram-positive aerobesand anaerobes. Clindamycin has no significant activity against gram-negative organisms. An

important role for clindamycin has emerged in the management of MRSA infections. Because of

its outstanding penetration into body fluids (exclud ing the CNS) and tissues and bone,

clindamycin can be utilized for therapy of serious infections caused by MRSA. Clindamycin isalso useful, usually in combination with a -lactam, in the management of invasive group A

streptococcus infections, and in the management of many anaerobic infections. There is a form

ofinducible clindamycin resistance exhibited by some strains of MRSA; therefore,consultation with the clinical microbiology laboratory is necessary before treating a serious


50/51

MRSA infection with clindamycin. Pseudomembranous colitis, a complication of clindamycin

therapy commonly encountered in adults, is seldom observed in pediatric patients.

Quinolones.

The fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin) are newerantimicrobials that inhibit bacterial DNA replication by binding to the topoisomerases of thetarget pathogen, inhibiting the bacterial enzyme, DNA gyrase, and DNA replication. This class

has very broad-spectrum activity against both gram-positive and gram-negative organisms. Some

of the fluoroquinolones exhibit activity against penicillin-resistant S. pneumoniae as well as

MRSA. These agents uniformly exhibit excellent activity against gram-negative pathogens,including the Enterobacteriaceae, and respiratory tract pathogens such asM. catarrhalis andH.

influenzae. Quinolones are also very active against pathogens associated with atypical

pneumonia, particularlyM. pneumoniae andL. pneumophila.

Although these agents are not approved for use in children, there is a reasonable body of

evidence that the fluoroquinolones are safe, well tolerated, and effective against a variety ofbacterial infections in children. Parenteral quinolones are appropriate for critically ill patients

with gram-negative infections. The use of oral quinolones in stable outpatients is also reasonable

for treatment of infections that would otherwise require parenteral antibiotics (P. aeruginosa soft

tissue infections such as osteochondritis) or selected genitourinary tract infections. However,they should be reserved for situations where no other oral antibiotic alternative is feasible. Where

they have been used frequently (typhoid fever) organisms may rapidly develop resistance.

Streptogramins and Oxazolidinones.

The emergence of highly resistant gram-positive organisms, in particular VRE, has necessitated

development of new classes of antibiotics to treat these infections. One class of antibiotics that ishighly useful for resistant gram-positive infections is the streptogramin class. The currently

licensed agent in this category, dalfopristin-quinupristin, is approved in a parenteral

formulation for patients >16 yr of age. It is appropriate for treatment of MRSA, coagulase-negative staphylococcus, penicillin-susceptible and penicillin-resistant pneumococcus, andvancomycin-resistantE. faecium but notE. faecalis.

Another licensed class of antibiotics for highly resistant gram-positive infections is the

oxazolidinone class. The prototype of this group is the linezolid, which is available in both oral

and parenteral formulations and is approved for use in pediatric patients. Its mechanism of action

is through inhibition of ribosomal protein synthesis. It is indicated for MRSA, VRE, coagulase-negative staphylococci, and penicillin-resistant pneumococci. There is little information on

dalfopristin-quinupristin and linezolid in treatment of infections involving the CNS, and neither

agent is approved for pediatric meningitis. Linezolid can cause anemia and thrombocytopenia

and is a monoamine oxidase inhibitor.

Daptomycin.


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Daptomycin is a cyclic lipopeptide with a spectrum of activity that includes virtually all gram-

positive organisms, includingE. faecalis andE. faecium (including VRE) and S. aureus

(including MRSA). The structure of daptomycin is a 13 member amino acid peptide linked to a10 carbon lipophilic tail, which results in a novel mechanism of action of disruption of the

bacterial membrane through the formation of transmembrane channels. These channels cause

leakage of intracellular ions leading to depolarizing the cellular membrane and inhibition ofmacromolecular synthesis. A theoretical advantage of daptomycin for serious infections is itsbactericidal activity against MRSA andEnterococcus. It is administered IV. Experience in

children is limited. Myopathy and elevations in creatine phosphokinase have been described.

Daptomycin is inactivated by surfactant and should not be used to treat pneumonia.

Miscellaneous Agents.

Although rarely used today because of safety concerns, chloramphenicol still occasionally playsa role in the management of pediatric infections, particularly those involving the CNS. Thisagent binds peptidyl transferase, a component of the 50S ribosome, inhibiting bacterial protein

synthesis. Metronidazole, which functions by disruption of DNA synthesis, has a unique role asan anti-anaerobic agent as well as possessing antiparasitic and anthelminthic activity. Rifampin,which inhibits bacterial RNA polymerase, has a major role in the management of tuberculosis

and is also of value for other bacterial infections in pediatric patients, usually used as a 2nd

(synergistic) agent forS. aureus infections or to eliminate nasopharyngeal colonization ofH.influenzae type b andN. meningitidis.

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