Ampicillin

Gram-positive organisms (Streptococcus spp.)

Susceptible Escherichia coli

Listeria monocytogenes

Empiric treatment for early- or late-onset (age >72 hrs) sepsis:

• ≤7 d old: 150 mg/kg/dose IV q12h
• >7 d old: 75 mg/kg/dose IV q6h

Treatment >48 h:

• Meningitis or no CSF obtained: 75 mg/kg/dose IV q6h
• Sepsis without meningitis: 75 mg/kg/dose IV q12h

Piperacillin

Pseudomonas aeruginosa Enterococcus spp.

Other Gram-negative enteric and anaerobes

PCN-susceptible Staphylococcus spp.

Streptococcus spp.

• ≤7 d: 50 mg/kg/dose q8h
• >7 d: 50 mg/kg/dose q6h

Moderate CSF penetration

Penicillin GK

GBS

Treponema pallidum

GBS meningitis:

• ≤7 d postnatal age: 450,000 units/kg/d divided every 8 h
• >7 d postnatal age: 450,000–500,000 units/kg/d divided every 4 h

Other GBS infections: 200,000 units/kg/d divided every 6 h

Nafcillin

Methicillin-sensitive Staphylococcus aureus

Non-CNS infections:

• <30 wk postmenstrual age (PMA):
  • ≤7 d: 25 mg/kg/dose q12h
  • >7 d: 25 mg/kg/dose q8h
• 30–37 wk PMA:
  • ≤7 d: 25 mg/kg/dose q12h
  • >7 d: 25 mg/kg/dose q8h
• >37 wk PMA:
  • ≤7 d: 25 mg/kg/dose q12h
  • >7 d: 25 mg/kg/dose q6h

Meningitis:

• Use 50 mg/kg/dose at same interval as listed above

Cleared primarily by the liver → monitor LFTs on treatment

Can cause interstitial nephritis → monitor renal function weekly on treatment

Can cause bone marrow suppression → monitor CBC weekly on therapy

Vancomycin

Aerobic and anaerobic Gram-positive cocci and bacilli

Methicillin-resistant S. aureus (MRSA)

Coagulase-negative staphylococci

Clostridium difficile

Bacillus spp.

Ampicillin-resistant Enterococcus

• <30 wk PMA:
  • ≤7 d: 20 mg/kg/dose IV q24h
  • >7 d: 20 mg/kg/dose IV q18h
• 30–37 wk PMA:
  • ≤7 d: 20 mg/kg/dose IV q18h
  • >7 d: 15 mg/kg/dose IV q12h
• >37 wk PMA:
  • ≤7 d: 15 mg/kg/dose IV q12h
  • >7 d: 15 mg/kg/dose IV q8h
• >44 wk PMA (meningitis):
  • 15 mg/kg/dose IV q6h

Only 10%–15% of serum concentration enters CSF.

Optimal serum concentration:

• Trough: 15–20 mcg/mL

Gentamicin, amikacin, tobramycin

Broad Gram-negative bacillus coverage

Synergistic against S. aureus, GBS, L. monocytogenes, enterococci

Gentamicin

• Indications: early- or late-onset sepsis (age >72 h); covers Gram-negative rods; use for synergy
  • <35 wk PMA: 3 mg/kg/dose IV q24h
  • ≥35wk PMA: 4 mg/kg/dose IV q24h
• If given >48 h (>2 doses), draw gentamicin trough before and peak level after the third dose. Monitor BUN/Cr:
  • Optimum levels: peak= 5–10 mcg/mL, trough = <1.5 mcg/mL
• For SYNERGY (against S. aureus, Enterococcus):
  • 1–1.5 mg/kg/dose IV q24h

Tobramycin

• <30 wk PMA:
  • ≤7 d: 3 mg/kg/dose q24h
  • >7 d: 3 mg/kg/dose q18h
• 30–37 wk PMA:
  • ≤7 d: 3 mg/kg/dose q18h
  • >7 d: 2.5 mg/kg/dose q12h
• >37 wk PMA:
  • ≤7 d: 2.5 mg/kg/dose q12h
  • >7 d: 2.5 mg/kg/dose q8h
• Optimum levels: peak = 8–10 mcg/mL; trough = <2 mcg/mL

Amikacin

• <30 wk PMA:
  • ≤7 d: 15 mg/kg/dose q24h
  • >7 d: 15 mg/kg/dose q18h
• 30–37 wk PMA:
  • ≤7 d: 15 mg/kg/dose q18h
  • >7 d: 15 mg/kg/dose q12h

CSF penetration depends on meningeal inflammation.

Monitor peak and trough levels, as these antibiotics can cause nephrotoxicity and ototoxicity.

• >37 wk PMA:
  • ≤7 d: 15 mg/kg/dose q12h
  • >7 d: 15 mg/kg/dose q8h
• Optimum levels: peak = 15–40 mcg/mL; trough = <10 mcg/mL

Clindamycin

Gram-positive cocci

Anaerobes (including Bacteroides fragilis)

• ≤37 wk PMA:
  • ≤7 d: 5 mg/kg/dose q8h
  • >7 d: 10 mg/kg/dose q8h
• >37 wk PMA:
  • 13 mg/kg/dose q8h

Poor CSF penetration

Cleared by the liver → monitor LFTs while on therapy

First-generation cephalosporins (cefazolin, cephalexin)

Susceptible Staphylococcus, Streptococcus, and pneumococci

Cefazolin:

• ≤7 d postnatal age:
  • 20 mg/kg/dose q12h
• >7 d postnatal age:
  • <2000 g: 20 mg/kg/dose q12h
  • >2000 g: 20 mg/kg/dose q8h

Poor CSF penetration

Second- generation cephalosporins (cefuroxime, cefoxitin, cefotetan, cefprozil)

Same as first generation

plus

Haemophilus influenzae

E. coli

Citrobacter

Klebsiella

Enterobacter cloacae

Improved activity over first-generation against β-lactamase–producing organisms

Little data in neonates, so use is limited

Third-generation cephalosporins (ceftriaxone, cefdinir, ceftazidime, cefotaxime, cefixime)

Gram-negative enterics

H. influenzae

Neisseria gonorrheae

Neisseria meningitidis

Cefotaxime:

• <1200 g, 0–4 wk: 50 mg/kg/dose q12h
• ≤7 d postnatal age:
  • 1200–2000 g: 50 mg/kg/dose q12h
  • >2000 g: 50 mg/kg/dose q8–12h
• >7 d postnatal age:
  • 1200–2000 g: 50 mg/kg/dose q8h
  • >2000 g: 150–200 mg/kg/d divided q6–8h

Ceftazidime:

• <7 d postnatal age:
  • 50 mg/kg/dose q12h
• 1–4 wk postnatal age:
  • 30–50 mg/kg/dose q8h

Ceftazidime can be used for adequate coverage of Pseudomonas aeruginosa.

Ceftazidime, cefotaxime, and ceftriaxone all achieve good CSF penetration.

Ceftriaxone displaces bilirubin from albumin, raising serum levels of free unconjugated bilirubin → not recommended for use in neonates except in treating gonococcal infection in nonjaundiced neonates. In jaundiced neonates, use cefotaxime.

Ceftriaxone

• ≤7 d postnatal age:
  • 50 mg/kg/d q24h
• >7 d postnatal age:
  • ≤2000 g: 50 mg/kg/d q24h
  • >2000 g: 50–75 mg/kg/d q24h
• Gonococcal prophylaxis:
  • 25–50 mg/kg as a single dose (maximum: 125 mg/dose)
• Gonococcal infection:
  • 25–50 mg/kg/d (maximum: 125 mg/dose) q24h for 7 d, up to 10–14 d if meningitis is documented

Macrolides (azithromycin)

Gram-positive bacteria

MRSA

Neisseria spp.

T. pallidum

Chlamydia trachomatis

Bordetella pertussis

Infants <6 mo:

• Pertussis (IV, oral): 10 mg/kg daily for 5 d

Oxazolidinone (linezolid)

Resistant Enterococcus faecium, S. aureus, Streptococcus pneumoniae

Neonates:

• 10 mg/kg/dose q8h

Preterm infants:

• 10 mg/kg/dose q12h

Use must be approved by infectious disease service

Carbapenems (meropenem)

Aerobic and anaerobic Gram-positive and Gram-negative bacteria

0–7 d postnatal age:

• Non-meningitis: 20 mg/kg/dose q12h
• Meningitis: 40 mg/kg/dose q12h

>7 d postnatal age:

• Weight 1200–2000 g:
  • Non-meningitis: 20 mg/kg/dose q12h
  • Meningitis: 40 mg/kg/dose q12h
• Weight >2000 g:
  • Non-meningitis: 20 mg/kg/dose q8h
  • Meningitis: 40 mg/kg/dose q8h

Use must be approved by infectious disease service

Good CSF penetration

Resistant organisms: Burkholderia cepacia, E. faecium, Stenotrophomonas maltophilia

<1 mo

L. monocytogenes, GBS, Enterobacteriaceae (E. coli)

Ampicillin and cefotaxime OR ampicillin and gentamicin

If Gram-negative bacilli, use cefotaxime instead of gentamicin, as gentamicin has poor CSF penetration.

14–21 d: GBS, L. monocytogenes

21 d: Enterobacteriaceae (cefotaxime + aminoglycoside)

1–3 mo

GBS, S. pneumoniae, N. meningitidis, H. influenzae, Enterobacteriaceae

Ampicillin and cefotaxime

10–14 d: S. pneumoniae

7 d: N. meningitidis

7–10 d: H. influenzae

>3 mo

S. pneumoniae, N. meningitidis, H. influenzae, above neonatal pathogens

Cefotaxime or ceftriaxone

Add vancomycin if possible PCN-resistant S. pneumoniae until susceptibilities return

Same as above

†Erythrocytes/mm3

≤1000

1001–1500

335 (0–1780)

407 (0–2450)

1465 (0–19,050)

1101 (0–9750)

808 (0–6850)

661 (0–3800)

Leukocytes/mm3

≤1000

1001–1500

3 (1–8)

4 (1–10)

4 (0–14)

7 (0–44)

4 (0–11)

8 (0–23)

Neutrophils (% of total leukocytes)

≤1000

1001–1500

11 (0–50)

4 (0–28)

8 (0–66)

10 (0–60)

2 (0–36)

11 (0–48)

‡Glucose (mg/dL)

≤1000

1001–1500

70 (41–89)

74 (50–96)

68 (33–217)

59 (39–109)

49 (29–90)

47 (37–76)

*Protein (mg/dL)

≤1000

1001–1500

162 (115–222)

136 (85–176)

159 (95–370)

137 (54–227)

137 (76–260)

122 (45–187)