antibiotik therapy nelson
TRANSCRIPT
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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
ACTION) AND DOSING COMMENTS
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
ACTION) AND DOSING COMMENTS
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
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
6 hr IV or IM).
Children: 100200
mg/kg/24 hr divided q6 hr IV or IM(meningitis: 200400
mg/kg/24 hr divided q
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
mg/kg/24 hr divided q
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
ACTION) AND DOSING COMMENTS
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
against gram-negative
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
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
68 hr IV or IM.
Children: 90120
mg/kg/24 hr divided q
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.
Neonates: Postnatal age
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
mg/kg/24 hr divided q
6 hr IV or IM.
Children: 400600
mg/kg/24 hr divided q
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
ACTION) AND DOSING COMMENTS
Capsule: 250,500 mg.
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.
Children: 2040mg/kg/24 hr divided q
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.
Suspension: 125 mg/5 mL,
250 mg/5 mL, 500 mg/5mL.
First-generation
cephalosporin active
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.
Drug interaction:Probenecid.
Cefazolin
Ancef, Kefzol.
Injection.
1st generation
cephalosporin active
against S. aureus,
Streptococcus, E. coli ,
Klebsiella, and
Proteus.
Neonates: Postnatal age
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
mg/kg/24 hr divided q
Caution:-Lactam safetyprofile (rash,
eosinophilia). Renally
eliminated. Does notadequately penetrate
CNS.
Drug interaction:
Probenecid.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q812 hr IV or IM.
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
cephalosporin active
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
ACTION) AND DOSING COMMENTS
>12,000 g: 150
mg/kg/24 hr divided q
8 hr IV or IM.
Children: 150 mg/kg/24
hr divided q 68 hr IV
or IM (meningitis: 200mg/kg/24 hr divided q
68 hr IV).
Adults: 12 g q 812 hr
IV or IM (max: 12 g/24hr).
Cefotetan disodium
Cefotan.
Injection.
2nd generation
cephalosporin active
against S. aureus,
Streptococcus, H.
in f luenzae, E. coli,
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
cephalosporin active
against S. aureus,
Streptococcus, H.
in f luenzae, E. coli,
Kl ebsiell a, Proteus,and Bacteroides.
Inactive against
Enterobacter.
Neonates: 70100mg/kg/24 hr divided q
812 hr IV or IM.
Cautions: Poor CNS
penetration; -Lactam
safety profile (rash,
eosinophilia). Renallyeliminated. Painful given
intramuscularly.
Drug interaction:Probenecid.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
Children: 80160
mg/kg/24 hr divided q
68 hr IV or IM.
Adults: 12 g q 68 hr
IV or IM (max dose: 12
g/24 hr).
Cefpodoxime proxetil
Vantin.
Tablet: 100 mg, 200 mg.
Suspension: 50 mg/5 mL,
100 mg/5 mL.
3rd generation
cephalosporin active
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.
Suspension: 125 mg/5 mL,
250 mg/5 mL.
2nd generation
cephalosporin active
against S. aureus,
Streptococcus, H.
I nf luenzae, E. coli, M .
catarr hal is, Klebsiella,and Proteus.
Children: 30 mg/kg/24
hr divided q 812 hr
PO.
Adults: 5001,000
Cautions:-Lactam
safety profile (rash,
eosinophilia). Renally
eliminated. Goodbioavailability; food does
not affect bioavailability.
Drug interaction:Probenecid.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
mg/24 hr divided q 12
hr PO (max dose: 1.5
g/24 hr).
Ceftazidime
Fortaz, Ceptaz, Tazicer,
Tazidime.
Injection.
3rd generation
cephalosporin active
against gram-positive
and gram-negative
pathogens including
Pseudomonas
aeruginosa.
Neonates: Postnatal age
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.
Children: 150 mg/kg/24
hr divided q 8 hr IV orIM (meningitis: 150
mg/kg/24 hr IV divided
q 8 hr).
Adults: 12 g q 812 hr
IV or IM (max: 812
g/24 hr).
Cautions:-Lactamsafety profile (rash,
eosinophilia). Renally
eliminated. Increasing
pathogen resistance
developing with long-term, widespread use.
Drug interaction:
Probenecid.
Ceftiaoxime
Cefizox.
Injection.
3rd generation
cephalosporin active
against gram-positive
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.
Drug interaction:Probenecid.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
Adults: 12 g q 68 hr
IV or IM (max dose: 12
g/24 hr).
Ceftriaxone sodium
Rocephin.
Injection.
3rd generation
cephalosporin active
against gram-positive
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).
Adults: 12 g q 24 hr
IV or IM (max dose: 4g/24 hr).
Cautions:-Lactamsafety profile (rash,
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
cephalosporin active
against S. aureus,
Streptococcus, H.
infl uenzae, E. coli , M .
catarr hal is, Klebsiella,
and Proteus.
Neonates: 40100
mg/kg/24 hr divided q12 hr IV or IM.
Children: 200240
mg/kg/24 hr divided q
8 hr IV or IM;POadministration:
Cautions:-Lactam
safety profile (rash,
eosinophilia).
Renally eliminated. Food
increases PO
bioavailability.
Drug interaction:
Probenecid.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
cephalosporin active
against S. aureus,
Streptococcus, E. coli ,
Klebsiella, and
Proteus.
Children: 25100
mg/kg/24 hr divided q
68 hr PO.
Adults: 250500 mg q6 hr PO (max dose: 4
g/24 hr).
Cautions:-Lactam
safety profile (rash,
eosinophilia). Renallyeliminated.
Drug interaction:
Probenecid.
Cephradine
Velosef
Capsule: 250,500 mg.Suspension: 125 mg/5 mL,
250 mg/5 mL.
1st generation
cephalosporin active
against S. aureus,
Streptococcus, E. coli ,Klebsiella, and
Proteus.
Children: 50100
mg/kg/24 hr divided q
612 hr PO.
Adults: 250500 mg q
612 hr PO (max dose:
4 g/24 hr).
Cautions:-Lactam
safety profile (rash,eosinophilia). Renally
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
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
12 hr IV.
Children: 5075
mg/kg/24 hr divided q
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,
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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.
Suspension: 125 mg/5 mL,
250 mg/5 mL.
Macrolide antibiotic
with activity against
S. aur eus,
Streptococcus, H.
in f luenzae, Legionella,
Mycoplasma, and C.
trachomatis.
Children: 15 mg/kg/24
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.
Suspension: 75 mg/5 mL.
Injection.
Topical solution, lotion,and gel.
Vaginal cream.
Protein synthesis
inhibitor active
against most gram-
positive aerobic and
anaerobic cocci except
Enterococcus.
Neonates: Postnatal age
7 days 2,000 g: 15 mg/kg/24
hr divided q 8 hr IV orIM; >7 days
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
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.
Capsule: 250,500 mg.
Suspension: 125 mg/5 mL.
Penicillinase-resistant
penicillin active
against S. aureusand
other gram-positive
cocci except
Enterococcusand
coagulase-negative
staphylococci.
Children: 50100
mg/kg/24 hr divided q
6 hr PO.
Adults: 250500 mg q
6 hr PO (max dose: 4
g/24 hr).
Cautions:-Lactamsafety profile (rash,
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
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
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
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
Dicloxacillin
Dynapen, Pathocil.
Capsule: 125,250,500 mg.
Suspension: 62.5 mg/5
mL.
Penicillinase-resistant
penicillin activeagainst S. aureusand
other gram-positive
cocci except
Enterococcusand
coagulase-negative
staphylococci.
Children: 12.5100
mg/kg/24 hr divided q
6 hr PO.
Adults: 125500 mg q
6 hr PO.
Cautions:-Lactamsafety profile (rash,
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.
Suspension: 25 mg/5 mL.
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.
Children: 25 mg/kg/24
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 (
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
positive cocci and
gram-negative bacilliincluding P.
aeruginosaand
anerobes. No activity
against
Stenotrophomonas
maltophilia.
Neonates: Postnatal age
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
mg/kg/24 hr divided q
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
against gram-positive
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.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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.
Suspension: 100 mg/5 mL,
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
safety profile (rash,eosinophilia). Renally
eliminated.
Drug interaction:Probenecid.
Meropenem
Merrem.
Injection.
Carbapenem
antibiotic active
against broad-
spectrum gram-
positive cocci and
gram-negative bacilli
including P.
aeruginosaand
anerobes. No activityagainst
Stenotrophomonas
maltophilia.
Children: 60 mg/kg/24
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.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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:
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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.
Neonates: Postnatal age
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.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
8 hr IV (meningitis:
200 mg/kg/24 hr
divided q 6 hr IV).
Children: 100200
mg/kg/24 hr divided q
46 hr IV.
Adults: 412 g/24 hr
divided q 46 hr IV
(max dose: 12 g/24 hr).
Nalidixic acid
NegGram.Tablet: 250,500,1,000 mg.
Suspension: 250 mg/5 mL.
1st generation
quinolone effective for
short-term treatment
of lower urinary tract
infections caused by
E. coli , Enterobacter ,
Klebsiella, and
Proteus.
Children: 5055mg/kg/24 hr divided q
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
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
Children: 50100
mg/kg/24 hr divided q
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.
Suspension: 25 mg/5 mL.
Effective in the
treatment of lower
urinary tract
infections caused by
gram-positive and
gram-negative
pathogens.
Children: 57 mg/kg/24
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.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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.
Capsule: 250,500 mg.
Suspension: 250 mg/5 mL.
Penicillinase-resistant
penicillin active
against S. aureusandother gram-positive
cocci except
Enterococcusand
coagulase-negative
staphylococci.
Neonates: Postnatal age
Cautions:-Lactam
safety profile (rash,
eosinophilia).
Moderate oral
bioavailability (3565%).
Primarily renallyeliminated.
Drug interaction:
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
46 hr IV.
Children: PO 50100
mg/kg/24 hr divided q
46 hr IV.
Adults: 212 g/24 hr
divided q 46 hr IV
(max dose: 12 g/24 hr).
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).
Neonates: Postnatal age
7 days 1,2002,000 g:
50,000 units/kg/24 hr
divided q 12 hr IV or
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.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
100,000 units/kg/24 hr
divided q 12 hr IV or
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:
100,000 units/kg/24 hr
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:
200,000 units/kg/24 hr
divided q 6 hr IV).
Children: 100,000
250,000 units/kg/24 hr
divided q 46 hr IV or
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.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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:
50,000 units/kg/24 hr
IM.
Children: 25,000
50,000 units/kg/24 hr
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
safety profile (rash,
eosinophilia), allergy,
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q48 hr PO.
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 ,
Enterobacter, Serr atia,
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
mg/kg/24 hr divided q
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
safety profile (rash,
eosinophilia); painfulgiven intramuscularly;
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
lactamase inhibitor
(tazobactam) activeagainst S. aureus, H.
in f luenzae, E. coli,
Enterobacter, Serr atia,
Acinetobacter, P.
aeruginosa, and
Bacteroides.
Children: 300400
mg/kg/24 hr divided q
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:
Neonates: 100mg/kg/24 hr divided q
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.
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
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.
Suspension: 500 mg/5 mL.
Sulfonamide
antibiotic used for the
treatment of otitis
media, chronic
bronchitis, and lowerurinary tract
infections due to
susceptible bacteria.
Children: 5060
mg/kg/24 hr divided q12 hr PO.
Adults: 1 g/dose q 12 hr
PO (max dose: 3 g/24
hr).
Cautions: Rash, Stevens-
Johnson syndrome,
nausea, leukopenia,
crystalluria. Renal and
hepatic elimination;avoid use with renal
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.
Suspension: 500 mg/5 mL.
Sulfonamide
antibiotic used for the
treatment of otitis
media, chronic
bronchitis, and lower
urinary tract
Cautions: Rash, Stevens-Johnson syndrome,
nausea, leukopenia,
crystalluria. Renal and
hepatic elimination;avoid use with renal
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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 ,
Enterobacter, Serr atia,
P. aeruginosa, and
Bacteroides.
Neonates: Postnatal age
7 days 7 days:
7 days 2,000 g: 300mg/kg/24 hr divided q
68 hr IV.
Children: 200400mg/kg/24 hr divided q
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).
Cautions:-Lactamsafety profile (rash,
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)
Cautions:-Lactamsafety profile (rash,
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
against gram-negative
bacilli, especially E.
coli, Klebsiella,
Enterobacter, Serr atia,
Proteus, and
Pseudomonas.
Neonates: Postnatal age
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
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
mg/kg/24 hr divided q
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)
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DRUG (TRADE NAMES,
FORMULATIONS)
INDICATIONS
(MECHANISM OF
ACTION) AND DOSING COMMENTS
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
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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
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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
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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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