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Systems-Based Treatment Tablea
SystemConditionCommon
Pathogens
Empiric Antibiotic
Therapy
Antibiotic
Duration
NotesKey Resources
Bloodstream Infection in Nonneonates (*uncomplicated)
*Defined by ≤3 days bacteremia in nonneutropenic host without complex source (eg, endocarditis, septic thrombophlebitis, osteomyelitis) or ongoing undrained purulent focus 
Common sources include vascular catheter-associated infection, urinary tract infection, intra-abdominal infection, pneumonia, skin/soft tissue infection Staphylococcus aureus MSSA
Cefazolin
OR
Oxacillin
OR
Nafcillin
MRSA
Vancomycin
OR
Linezolid
OR
Daptomycin
OR
Ceftaroline 
14 days from first negative blood culture Vascular catheter removal generally recommended for persistent hemodynamic instability or ongoing (≥3 days) bacteremia RCTs for duration of gram-negative BSI:
Yahav et al1
von Dach et al2
Molina et al3
Observational studies:
Sutton et al4
Punjabi et al5
Tamma et al6
Heil et al7
Mponponsuo et al8
Tamma et al9 
Enterococcus faecalis Ampicillin 7 days from first negative blood culture 
Enterococcus faecium Vancomycin OR
Linezolid OR Daptomycin 
7 days from first negative blood culture 
Enterobacterales (eg, Escherichia coli, Klebsiella species, Enterobacter species) Choice depends on results of antibiotic susceptibility testing 7 days from first negative blood culture Duration of therapy is regardless of whether vascular catheter is removed, and should not be extended solely based on presence of antibiotic resistance or retained vascular catheter
Duration of therapy is based on duration of active therapy (ie, adequate dose and antibiotic susceptibility)
Transition to oral antibiotics may be considered for uncomplicated gram-negative bacteremia if all of the following criteria are met: (1) susceptibility to an appropriate, highly available oral agent is demonstrated; (2) the patient is hemodynamically stable; (3) reasonable source control measures have occurred; (4) intestinal absorption is intact; and (5) there is confidence in patient adherence 
Pseudomonas aeruginosa Choice depends on results of antibiotic susceptibility testing 7 days from first negative blood culture 
Coagulase-negative Staphylococcus
(not including Staphylococcus Lugdunensis, which should be managed like S aureus
Vancomycin
OR
Oxacillin (if susceptible) 
5–7 days from first negative blood culture, OR observation following removal of foreign body source (eg, catheter) A single positive culture absent hardware generally reflects skin contamination 
Bone/Joint Osteomyelitis (acute, hematogenous) S aureus

Streptococcus pyogenes

Kingella kingae 
Mild-Moderate
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and low suspicion of MRSA
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and high suspicion of MRSA
Vancomycin
OR
Clindamycin
OR
Linezolid
OR
Daptomycin 
3–4 wk
Chronic osteomyelitis typically requires more prolonged antibiotic treatment and may require consideration of alternate antibiotic choice 
Kingella infection not effectively treated by clindamycin and not reliably susceptible to oxacillin/nafcillin
Early switch to oral route recommended with clinical improvement, even for patients with transient bacteremia
For empiric management of children with osteomyelitis and severe sepsis, combination therapy of vancomycin PLUS oxacillin/nafcillin can be considered 
Woods et al10 
Septic arthritis S aureus
S pyogenes
K kingae 
Mild-Moderate
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and low suspicion of MRSA
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and high suspicion of MRSA
Vancomycin
OR
Clindamycin
OR
Linezolid
OR
Daptomycin 
2–3 wk Kingella not effectively treated by clindamycin and not reliably susceptible to oxacillin/nafcillin
Early switch to oral route recommended with clinical improvement, even for patients with transient bacteremia 
Woods et al11 
Central Nervous System Meningitis (non-neonates) Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae Ceftriaxone
PLUS
Vancomycin 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture and susceptibility results
S pneumoniae: 10–14 days
H influenzae: 7–10 days
N meningitidis: 5–7 days 
Longer courses are necessary for patients with parenchymal brain infection (cerebritis, rhombencephalitis, brain abscess)
Dexamethasone is beneficial for treatment of infants and children with Hib meningitis to diminish the risk of hearing loss, if administered before or concurrently with the first dose of antimicrobial agent(s)
For all children with bacterial meningitis presumed to be caused by S pneumoniae, vancomycin should be administered in addition to ceftriaxone because of the possibility of resistant S pneumoniae
Consider adding acyclovir for patients with concurrent encephalitis 
Streptococcus pneumoniae (Pneumococcal) Infections, p 810
Meningococcal Infections, p 585
Haemophilus influenzae Infections, p 400 
Ear, Nose, and Throat Mastoiditis S pneumoniae
S pyogenes
S aureus
H influenzae
Also consider for chronic:
Microaerophilic streptococci
Fusobacterium
P aeruginosa 
Consider surgical drainage/excision
Ampicillin-sulbactam OR Ceftriaxone
(Allergyb: Clindamycin)
If follows chronic AOM:
Cefepime
OR
Levofloxacin
Consider MRSA
based on local prevalence 
2–4 wk depending on adequate débridement, intracranial extension, extent of osteomyelitis, associated thrombosis Transition to oral with clinical improvement
Ampicillin-sulbactam may not be optimal for intracranial infections 
Haemophilus influenzae Infections, p 400
Fusobacterium Infections, p 388
Pseudomonas aeruginosa Infections, p 697
Staphylococcus aureus, p 767
Group A Streptococcal Infections, p 785
Non-Group A or B Streptococcal and Enterococcal Infections, p 806
Streptococcus pneumoniae (Pneumococcal) Infections, p 810 
Acute sinusitis S pneumoniae
H influenzae
Moraxella catarrhalis 
Amoxicillin
OR
Amoxicillin-clavulanate
(Allergyb: Clindamycin OR Levofloxacin) 
5–7 days Diagnosis of acute bacterial sinusitis requires the presence of one of the following criteria: (1) persistent nasal discharge or daytime cough without evidence of clinical improvement for ≥10 days; consider watchful waiting in this scenario (2) worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement (3) temperature ≥39°C with purulent nasal discharge and/or facial pain for at least 3 consecutive days Haemophilus influenzae Infections, p 400
Moraxella catarrhalis Infections, p 604
Streptococcus pneumoniae (Pneumococcal) Infections, p 810
Chow et al12
Wald et al13 
Acute otitis media S pneumoniae
H influenzae
M catarrhalis 
Amoxicillin
OR
Amoxicillin-clavulanatec
(Allergy: Cefdinir OR Cefpodoxime OR Cefuroxime OR Ceftriaxone for 1 (first occurrence) to 3 (treatment failure) days 
>6 y: 5 days
2–5 y: 7 days
<2 y or severe symptoms: 10 days 
Consider observation without antibiotics for 48–72 hours for children 24 months or older without severe symptoms; if symptoms persist or worsen, use same antibiotic recommendations as for those receiving immediate therapy
Consider S aureus and Pseudomonas infection for chronic otitis media 
Haemophilus influenzae Infections, p 400
Moraxella catarrhalis Infections, p 604
Streptococcus pneumoniae (Pneumococcal) Infections, p 810
Lieberthal et al14
Rosenfeld et al15 
Streptococcal pharyngitis S pyogenes First line:
Penicillin
OR
Amoxicillin
(Allergyb: Cephalexin OR Clindamycin OR Azithromycin) 
10 days Children with rhinorrhea, cough, hoarseness, or oral ulcers should not be tested or treated for GAS infection; testing also generally is not recommended for children <3 y
Management of recurrent GAS pharyngitis and pharyngeal carriers is detailed in Group A Streptococcal Infections (p 785)
Tetracyclines, TMP-SMX, and fluoroquinolones should not be used for treating GAS pharyngitis
Return to school after afebrile and ≥12 h of antibiotic therapy 
Group A Streptococcal Infections, p 785
Shulman et al16 
Retropharyngeal abscess S aureus
S pyogenes
Anaerobes
Streptococcus anginosus
H influenzae (often polymicrobial) 
Mild-moderate:
Ampicillin/sulbactam
OR
Clindamycin
Severe:
Ampicillin/sulbactam
PLUS EITHER
Vancomycin OR
Linezolid 
14 days Longer duration of therapy may be required for complex infections with insufficient source control  
Genitourinary UTI - pyelonephritis E coli
Klebsiella species
Proteus species
Enterobacter species
Citrobacter species
Enterococcus species
Staphylococcus saprophyticus 
Cephalexin
OR
TMP-SMX
OR
Ampicillin PLUS Gentamicin
OR
Ceftriaxone
OR
Ciprofloxacin 
7–10 days (hospitalized)
5–10 days (outpatient)
3–5 days (simple cystitis in adolescents)
Longer durations may be required for complicated cases such as renal abscess without drainage 
Drug selection should be based on local antibiogram or patient’s prior urine isolates
Initial short course of IV therapy (2–4 days) is as effective as longer courses of IV therapy
Avoid nitrofurantoin for upper urinary tract infection or bacteremia 
Mattoo et al17
Gupta et al18 
Intra-abdominal Intra-abdominal infection E coli
Anaerobes
Klebsiella species (often polymicrobial) 
Drainage
Mild-moderate:
Ceftriaxone
PLUS
Metronidazole
Severe or hospital onset:
Piperacillin-tazobactam
OR
Ciprofloxacin PLUS
Metronidazole 
4–7 days (from source control) May need longer duration if insufficient source control
Mild-moderate infection includes complicated appendicitis with rupture, absent sepsis 
Mazuski et al19 
Neonatal Fever (Term Neonates) Suspected UTI E coli
Enterococcus species
GBS 
Ampicillin
PLUS
Gentamicin 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture results   
Unclear source GBS
E coli
HSV 
Neonates 0–7 days of age:
Ampicillin
PLUS
Gentamicin
Neonates 8–28 days of age:
Ampicillin PLUS Gentamicin
OR
Ampicillin PLUS Cefotaxime (Ceftazidime or Cefepime if Cefotaxime not available) 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture results Consider adding empiric acyclovir with surface, blood, and CSF HSV sampling for infants at increased risk of HSV, including the presence of skin vesicles, seizures, CSF pleocytosis with a negative Gram stain, leukopenia, hepatitis, thrombocytopenia, hypothermia, mucous membrane ulcers, or maternal history of genital HSV lesions or fever from 48 hours before to 48 hours after delivery. For further discussion of HSV, see Herpes Simplex (p 467).  
Suspected meningitis GBS
E coli
HSV 
Neonates 0–7 days of age:
Ampicillin
PLUS
Gentamicin
(some experts will add a third or fourth generation cephalosporin if the cerebrospinal fluid gram stain shows gram-negative organisms)
Neonates 8–28 days of age:
Ampicillin
PLUS
Cefotaxime (Ceftazidime or Cefepime if Cefotaxime not available)
(some experts will add an aminoglycoside if the cerebrospinal fluid Gram stain shows gram-negative organisms) 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture results
GBS:
14 days penicillin G
E coli:
21 days of non-aminoglycoside antibiotic to which isolate is susceptible 
Some experts suggest repeat lumbar puncture to document CSF sterility
Consider adding empiric acyclovir with surface, blood, and CSF HSV sampling for infants at increased risk of HSV, including the presence of skin vesicles, seizures, CSF pleocytosis with a negative Gram stain, leukopenia, hepatitis, thrombocytopenia, hypothermia, mucous membrane ulcers, or maternal history of genital HSV lesions or fever from 48 hours before to 48 hours after delivery. For further discussion of HSV, see Herpes Simplex (p 467). 
Puopolo et al20
Puopolo et al21 
Ophthalmologic Preseptal cellulitis (ie, nonsinus origin) S pyogenes
S aureus 
Mild-moderate:
Cefazolin OR
Cephalexin
(Allergyb:
Clindamycin)
Severe:
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin 
5–7 days Switch to oral with 24 hours improvement in fever, swelling, and erythema
Consider empiric MRSA coverage if high local MRSA rates 
 
Orbital cellulitis S aureus
S pneumoniae
Anaerobes
S anginosus
H influenzae
M catarrhalis
S pyogenes 
Surgical drainage (if abscess): Ampicillin/sulbactam
(Allergyb: Clindamycin)
Severe: Add
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin 
10–14 days
May extend to 3–4 wk with extensive bone involvement and/or insufficient source control 
Consider empiric MRSA coverage if high local MRSA rates  
Respiratory Community-acquired pneumonia (CAP) S pneumoniae
Mycoplasma pneumoniae
S pyogenes
S aureus
H influenzae
M catarrhalis
Respiratory viruses, including influenza virus, adenovirus, parainfluenza virus, respiratory syncytial virus, coronaviruses, human metapneumovirus 
Amoxicillin OR Ampicillin OR Penicillin for fully immunized patients in regions without high prevalence of PCN-resistant pneumococcus
(Allergyb: Clindamycin OR Levofloxacin)
Ceftriaxone for hospitalized patients in regions with high levels PCN-resistant pneumococcus
Add macrolide if atypical pathogen (eg, Mycoplasma or Chlamydia species) suspected
Add Vancomycin OR Clindamycin OR Linezolid if MRSA suspected 
5 days for uncomplicated CAP with resolution of fever, tachypnea, and supplemental oxygen requirement
May extend duration when complicated by empyema, necrotizing pneumonia, or pulmonary abscess 
Respiratory viruses cause the majority of CAP, especially in young children; thus, antibiotic therapy may not be indicated for all patients
Early switch to oral route encouraged when tolerated
Transient S pneumoniae bacteremia in otherwise uncomplicated pneumonia does not warrant prolonged or IV antibiotic therapy
Consider S aureus superinfection in patients with influenza 
Bradley et al22 
Skin and Soft Tissue Infections Cellulitis (nonpurulent) S pyogenes
S aureus 
Mild-moderate:
Cefazolin
OR
Oxacillin/nafcillin
OR
Cephalexin
(Allergyb: Clindamycin
OR
TMP/SMX
OR
Doxycycline)
Severe:
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin
Necrotizing fasciitis:
Surgical débridement
B-lactam PLUS
Clindamycin (+/- Vancomycin) 
5–7 days
Tailor duration based on resolution of signs and symptoms 
For bite wounds, see p 202
Necrotizing fasciitis may require gram-negative or anaerobic coverage in the correct clinical scenario
For severe infections, consider coverage of MRSA based on local prevalence 
Staphylococcus aureus, p 767
Group A Streptococcal Infections, p 785
Bacteroides, Prevotella, and Other Anaerobic Gram-Negative Bacilli Infections, p 261
Stevens et al23 
Purulent cellulitis/Abscess S aureus Drainage
Mild-moderate:
Cefazolin/cephalexin
OR
TMP/SMX
OR
Clindamycin
OR
Doxycycline
Consider MRSA based on local prevalence
Severe:
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin 
5–7 days
Tailor duration based on resolution of signs and symptoms
Surgical drainage alone may be adequate for small, completely drained abscesses 
Conversion to oral antibiotic therapy after transientdS aureus bacteremia with source control is appropriate but might warrant more prolonged therapy Staphylococcus aureus, p 767
Stevens et al23 
Lymphadenitis Acute/unilateral:
S pyogenes
S aureus
Subacute/chronic:
Bartonella species
Nontuberculous mycobacteria (NTM) 
For acute/unilateral lymphadenitis: Consider surgical drainage
Cefazolin/Cephalexin
(Allergyb: Clindamycin)
Consider MRSA based on local prevalence 
5–7 days
Tailor duration based on resolution of signs and symptoms 
For management of NTM or Bartonella infection, please see those chapters (p 920 and p 263)
Bacterial adenitis is typically unilateral; bilateral disease is typically viral in etiology 
Bartonella henselae (Cat-Scratch Disease), p 263
Staphylococcus aureus, p 767
Group A Streptococcal Infections, p 785
Nontuberculous Mycobacteria, p 920 
SystemConditionCommon
Pathogens
Empiric Antibiotic
Therapy
Antibiotic
Duration
NotesKey Resources
Bloodstream Infection in Nonneonates (*uncomplicated)
*Defined by ≤3 days bacteremia in nonneutropenic host without complex source (eg, endocarditis, septic thrombophlebitis, osteomyelitis) or ongoing undrained purulent focus 
Common sources include vascular catheter-associated infection, urinary tract infection, intra-abdominal infection, pneumonia, skin/soft tissue infection Staphylococcus aureus MSSA
Cefazolin
OR
Oxacillin
OR
Nafcillin
MRSA
Vancomycin
OR
Linezolid
OR
Daptomycin
OR
Ceftaroline 
14 days from first negative blood culture Vascular catheter removal generally recommended for persistent hemodynamic instability or ongoing (≥3 days) bacteremia RCTs for duration of gram-negative BSI:
Yahav et al1
von Dach et al2
Molina et al3
Observational studies:
Sutton et al4
Punjabi et al5
Tamma et al6
Heil et al7
Mponponsuo et al8
Tamma et al9 
Enterococcus faecalis Ampicillin 7 days from first negative blood culture 
Enterococcus faecium Vancomycin OR
Linezolid OR Daptomycin 
7 days from first negative blood culture 
Enterobacterales (eg, Escherichia coli, Klebsiella species, Enterobacter species) Choice depends on results of antibiotic susceptibility testing 7 days from first negative blood culture Duration of therapy is regardless of whether vascular catheter is removed, and should not be extended solely based on presence of antibiotic resistance or retained vascular catheter
Duration of therapy is based on duration of active therapy (ie, adequate dose and antibiotic susceptibility)
Transition to oral antibiotics may be considered for uncomplicated gram-negative bacteremia if all of the following criteria are met: (1) susceptibility to an appropriate, highly available oral agent is demonstrated; (2) the patient is hemodynamically stable; (3) reasonable source control measures have occurred; (4) intestinal absorption is intact; and (5) there is confidence in patient adherence 
Pseudomonas aeruginosa Choice depends on results of antibiotic susceptibility testing 7 days from first negative blood culture 
Coagulase-negative Staphylococcus
(not including Staphylococcus Lugdunensis, which should be managed like S aureus
Vancomycin
OR
Oxacillin (if susceptible) 
5–7 days from first negative blood culture, OR observation following removal of foreign body source (eg, catheter) A single positive culture absent hardware generally reflects skin contamination 
Bone/Joint Osteomyelitis (acute, hematogenous) S aureus

Streptococcus pyogenes

Kingella kingae 
Mild-Moderate
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and low suspicion of MRSA
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and high suspicion of MRSA
Vancomycin
OR
Clindamycin
OR
Linezolid
OR
Daptomycin 
3–4 wk
Chronic osteomyelitis typically requires more prolonged antibiotic treatment and may require consideration of alternate antibiotic choice 
Kingella infection not effectively treated by clindamycin and not reliably susceptible to oxacillin/nafcillin
Early switch to oral route recommended with clinical improvement, even for patients with transient bacteremia
For empiric management of children with osteomyelitis and severe sepsis, combination therapy of vancomycin PLUS oxacillin/nafcillin can be considered 
Woods et al10 
Septic arthritis S aureus
S pyogenes
K kingae 
Mild-Moderate
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and low suspicion of MRSA
Cefazolin
OR
Oxacillin
OR
Nafcillin
Severe and high suspicion of MRSA
Vancomycin
OR
Clindamycin
OR
Linezolid
OR
Daptomycin 
2–3 wk Kingella not effectively treated by clindamycin and not reliably susceptible to oxacillin/nafcillin
Early switch to oral route recommended with clinical improvement, even for patients with transient bacteremia 
Woods et al11 
Central Nervous System Meningitis (non-neonates) Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae Ceftriaxone
PLUS
Vancomycin 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture and susceptibility results
S pneumoniae: 10–14 days
H influenzae: 7–10 days
N meningitidis: 5–7 days 
Longer courses are necessary for patients with parenchymal brain infection (cerebritis, rhombencephalitis, brain abscess)
Dexamethasone is beneficial for treatment of infants and children with Hib meningitis to diminish the risk of hearing loss, if administered before or concurrently with the first dose of antimicrobial agent(s)
For all children with bacterial meningitis presumed to be caused by S pneumoniae, vancomycin should be administered in addition to ceftriaxone because of the possibility of resistant S pneumoniae
Consider adding acyclovir for patients with concurrent encephalitis 
Streptococcus pneumoniae (Pneumococcal) Infections, p 810
Meningococcal Infections, p 585
Haemophilus influenzae Infections, p 400 
Ear, Nose, and Throat Mastoiditis S pneumoniae
S pyogenes
S aureus
H influenzae
Also consider for chronic:
Microaerophilic streptococci
Fusobacterium
P aeruginosa 
Consider surgical drainage/excision
Ampicillin-sulbactam OR Ceftriaxone
(Allergyb: Clindamycin)
If follows chronic AOM:
Cefepime
OR
Levofloxacin
Consider MRSA
based on local prevalence 
2–4 wk depending on adequate débridement, intracranial extension, extent of osteomyelitis, associated thrombosis Transition to oral with clinical improvement
Ampicillin-sulbactam may not be optimal for intracranial infections 
Haemophilus influenzae Infections, p 400
Fusobacterium Infections, p 388
Pseudomonas aeruginosa Infections, p 697
Staphylococcus aureus, p 767
Group A Streptococcal Infections, p 785
Non-Group A or B Streptococcal and Enterococcal Infections, p 806
Streptococcus pneumoniae (Pneumococcal) Infections, p 810 
Acute sinusitis S pneumoniae
H influenzae
Moraxella catarrhalis 
Amoxicillin
OR
Amoxicillin-clavulanate
(Allergyb: Clindamycin OR Levofloxacin) 
5–7 days Diagnosis of acute bacterial sinusitis requires the presence of one of the following criteria: (1) persistent nasal discharge or daytime cough without evidence of clinical improvement for ≥10 days; consider watchful waiting in this scenario (2) worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement (3) temperature ≥39°C with purulent nasal discharge and/or facial pain for at least 3 consecutive days Haemophilus influenzae Infections, p 400
Moraxella catarrhalis Infections, p 604
Streptococcus pneumoniae (Pneumococcal) Infections, p 810
Chow et al12
Wald et al13 
Acute otitis media S pneumoniae
H influenzae
M catarrhalis 
Amoxicillin
OR
Amoxicillin-clavulanatec
(Allergy: Cefdinir OR Cefpodoxime OR Cefuroxime OR Ceftriaxone for 1 (first occurrence) to 3 (treatment failure) days 
>6 y: 5 days
2–5 y: 7 days
<2 y or severe symptoms: 10 days 
Consider observation without antibiotics for 48–72 hours for children 24 months or older without severe symptoms; if symptoms persist or worsen, use same antibiotic recommendations as for those receiving immediate therapy
Consider S aureus and Pseudomonas infection for chronic otitis media 
Haemophilus influenzae Infections, p 400
Moraxella catarrhalis Infections, p 604
Streptococcus pneumoniae (Pneumococcal) Infections, p 810
Lieberthal et al14
Rosenfeld et al15 
Streptococcal pharyngitis S pyogenes First line:
Penicillin
OR
Amoxicillin
(Allergyb: Cephalexin OR Clindamycin OR Azithromycin) 
10 days Children with rhinorrhea, cough, hoarseness, or oral ulcers should not be tested or treated for GAS infection; testing also generally is not recommended for children <3 y
Management of recurrent GAS pharyngitis and pharyngeal carriers is detailed in Group A Streptococcal Infections (p 785)
Tetracyclines, TMP-SMX, and fluoroquinolones should not be used for treating GAS pharyngitis
Return to school after afebrile and ≥12 h of antibiotic therapy 
Group A Streptococcal Infections, p 785
Shulman et al16 
Retropharyngeal abscess S aureus
S pyogenes
Anaerobes
Streptococcus anginosus
H influenzae (often polymicrobial) 
Mild-moderate:
Ampicillin/sulbactam
OR
Clindamycin
Severe:
Ampicillin/sulbactam
PLUS EITHER
Vancomycin OR
Linezolid 
14 days Longer duration of therapy may be required for complex infections with insufficient source control  
Genitourinary UTI - pyelonephritis E coli
Klebsiella species
Proteus species
Enterobacter species
Citrobacter species
Enterococcus species
Staphylococcus saprophyticus 
Cephalexin
OR
TMP-SMX
OR
Ampicillin PLUS Gentamicin
OR
Ceftriaxone
OR
Ciprofloxacin 
7–10 days (hospitalized)
5–10 days (outpatient)
3–5 days (simple cystitis in adolescents)
Longer durations may be required for complicated cases such as renal abscess without drainage 
Drug selection should be based on local antibiogram or patient’s prior urine isolates
Initial short course of IV therapy (2–4 days) is as effective as longer courses of IV therapy
Avoid nitrofurantoin for upper urinary tract infection or bacteremia 
Mattoo et al17
Gupta et al18 
Intra-abdominal Intra-abdominal infection E coli
Anaerobes
Klebsiella species (often polymicrobial) 
Drainage
Mild-moderate:
Ceftriaxone
PLUS
Metronidazole
Severe or hospital onset:
Piperacillin-tazobactam
OR
Ciprofloxacin PLUS
Metronidazole 
4–7 days (from source control) May need longer duration if insufficient source control
Mild-moderate infection includes complicated appendicitis with rupture, absent sepsis 
Mazuski et al19 
Neonatal Fever (Term Neonates) Suspected UTI E coli
Enterococcus species
GBS 
Ampicillin
PLUS
Gentamicin 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture results   
Unclear source GBS
E coli
HSV 
Neonates 0–7 days of age:
Ampicillin
PLUS
Gentamicin
Neonates 8–28 days of age:
Ampicillin PLUS Gentamicin
OR
Ampicillin PLUS Cefotaxime (Ceftazidime or Cefepime if Cefotaxime not available) 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture results Consider adding empiric acyclovir with surface, blood, and CSF HSV sampling for infants at increased risk of HSV, including the presence of skin vesicles, seizures, CSF pleocytosis with a negative Gram stain, leukopenia, hepatitis, thrombocytopenia, hypothermia, mucous membrane ulcers, or maternal history of genital HSV lesions or fever from 48 hours before to 48 hours after delivery. For further discussion of HSV, see Herpes Simplex (p 467).  
Suspected meningitis GBS
E coli
HSV 
Neonates 0–7 days of age:
Ampicillin
PLUS
Gentamicin
(some experts will add a third or fourth generation cephalosporin if the cerebrospinal fluid gram stain shows gram-negative organisms)
Neonates 8–28 days of age:
Ampicillin
PLUS
Cefotaxime (Ceftazidime or Cefepime if Cefotaxime not available)
(some experts will add an aminoglycoside if the cerebrospinal fluid Gram stain shows gram-negative organisms) 
These are empiric recommendations; specific choice and duration of antibiotic therapy should be guided by culture results
GBS:
14 days penicillin G
E coli:
21 days of non-aminoglycoside antibiotic to which isolate is susceptible 
Some experts suggest repeat lumbar puncture to document CSF sterility
Consider adding empiric acyclovir with surface, blood, and CSF HSV sampling for infants at increased risk of HSV, including the presence of skin vesicles, seizures, CSF pleocytosis with a negative Gram stain, leukopenia, hepatitis, thrombocytopenia, hypothermia, mucous membrane ulcers, or maternal history of genital HSV lesions or fever from 48 hours before to 48 hours after delivery. For further discussion of HSV, see Herpes Simplex (p 467). 
Puopolo et al20
Puopolo et al21 
Ophthalmologic Preseptal cellulitis (ie, nonsinus origin) S pyogenes
S aureus 
Mild-moderate:
Cefazolin OR
Cephalexin
(Allergyb:
Clindamycin)
Severe:
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin 
5–7 days Switch to oral with 24 hours improvement in fever, swelling, and erythema
Consider empiric MRSA coverage if high local MRSA rates 
 
Orbital cellulitis S aureus
S pneumoniae
Anaerobes
S anginosus
H influenzae
M catarrhalis
S pyogenes 
Surgical drainage (if abscess): Ampicillin/sulbactam
(Allergyb: Clindamycin)
Severe: Add
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin 
10–14 days
May extend to 3–4 wk with extensive bone involvement and/or insufficient source control 
Consider empiric MRSA coverage if high local MRSA rates  
Respiratory Community-acquired pneumonia (CAP) S pneumoniae
Mycoplasma pneumoniae
S pyogenes
S aureus
H influenzae
M catarrhalis
Respiratory viruses, including influenza virus, adenovirus, parainfluenza virus, respiratory syncytial virus, coronaviruses, human metapneumovirus 
Amoxicillin OR Ampicillin OR Penicillin for fully immunized patients in regions without high prevalence of PCN-resistant pneumococcus
(Allergyb: Clindamycin OR Levofloxacin)
Ceftriaxone for hospitalized patients in regions with high levels PCN-resistant pneumococcus
Add macrolide if atypical pathogen (eg, Mycoplasma or Chlamydia species) suspected
Add Vancomycin OR Clindamycin OR Linezolid if MRSA suspected 
5 days for uncomplicated CAP with resolution of fever, tachypnea, and supplemental oxygen requirement
May extend duration when complicated by empyema, necrotizing pneumonia, or pulmonary abscess 
Respiratory viruses cause the majority of CAP, especially in young children; thus, antibiotic therapy may not be indicated for all patients
Early switch to oral route encouraged when tolerated
Transient S pneumoniae bacteremia in otherwise uncomplicated pneumonia does not warrant prolonged or IV antibiotic therapy
Consider S aureus superinfection in patients with influenza 
Bradley et al22 
Skin and Soft Tissue Infections Cellulitis (nonpurulent) S pyogenes
S aureus 
Mild-moderate:
Cefazolin
OR
Oxacillin/nafcillin
OR
Cephalexin
(Allergyb: Clindamycin
OR
TMP/SMX
OR
Doxycycline)
Severe:
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin
Necrotizing fasciitis:
Surgical débridement
B-lactam PLUS
Clindamycin (+/- Vancomycin) 
5–7 days
Tailor duration based on resolution of signs and symptoms 
For bite wounds, see p 202
Necrotizing fasciitis may require gram-negative or anaerobic coverage in the correct clinical scenario
For severe infections, consider coverage of MRSA based on local prevalence 
Staphylococcus aureus, p 767
Group A Streptococcal Infections, p 785
Bacteroides, Prevotella, and Other Anaerobic Gram-Negative Bacilli Infections, p 261
Stevens et al23 
Purulent cellulitis/Abscess S aureus Drainage
Mild-moderate:
Cefazolin/cephalexin
OR
TMP/SMX
OR
Clindamycin
OR
Doxycycline
Consider MRSA based on local prevalence
Severe:
Vancomycin
OR
Linezolid
OR
Ceftaroline
OR
Daptomycin 
5–7 days
Tailor duration based on resolution of signs and symptoms
Surgical drainage alone may be adequate for small, completely drained abscesses 
Conversion to oral antibiotic therapy after transientdS aureus bacteremia with source control is appropriate but might warrant more prolonged therapy Staphylococcus aureus, p 767
Stevens et al23 
Lymphadenitis Acute/unilateral:
S pyogenes
S aureus
Subacute/chronic:
Bartonella species
Nontuberculous mycobacteria (NTM) 
For acute/unilateral lymphadenitis: Consider surgical drainage
Cefazolin/Cephalexin
(Allergyb: Clindamycin)
Consider MRSA based on local prevalence 
5–7 days
Tailor duration based on resolution of signs and symptoms 
For management of NTM or Bartonella infection, please see those chapters (p 920 and p 263)
Bacterial adenitis is typically unilateral; bilateral disease is typically viral in etiology 
Bartonella henselae (Cat-Scratch Disease), p 263
Staphylococcus aureus, p 767
Group A Streptococcal Infections, p 785
Nontuberculous Mycobacteria, p 920 

AAP indicates American Academy of Pediatrics; AOM, acute otitis media; CAP, community-acquired pneumonia; CSF, cerebrospinal fluid; GAS, group A Streptococcus; GBS, group B Streptococcus; HSV, herpes simplex virus; IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; NTM, nontuberculous mycobacteria; PCN, penicillin; TMP-SMX, trimethoprim-sulfamethoxazole; UTI, urinary tract infection.

Boldface indicates primary pathogen(s) targeted by empiric antibiotic therapy.

aEmpiric antibiotic selection should be based on local antibiotic resistance prevalence.

bAntibiotic allergy includes anaphylaxis or cutaneous response (eg, hives) within 6 hours of drug exposure, or severe cutaneous reaction at any time (eg, Steven Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], drug reaction w/eosinophilia and systemic symptoms [DRESS], erythema multiforme, or serum sickness like reaction). Isolated gastrointestinal tract symptoms, family history of drug allergy, or later-onset nonspecific maculopapular rash do not indicate IgE-mediated drug allergy (see www.allergyparameters.org/parameters-and-guidelines).

cAmoxicillin-clavulanate should be used if the patient has received amoxicillin treatment in last 30 days, has concurrent purulent conjunctivitis, or has a history of recurrent AOM unresponsive to amoxicillin.

dOral antibiotics may be considered for bacteremia if bacteremia clears within 72 hours of source control and initiation of effective antibiotic therapy.

1Yahav D, Franceschini E, Koppel F, et al. Seven versus 14 days of antibiotic therapy for uncomplicated gram-negative bacteremia: a noninferiority randomized controlled trial. Clin Infect Dis. 2019;69(7):1091-1098

2von Dach E, Albrich WC, Brunel AS, et al. Effect of C-reactive protein-guided antibiotic treatment duration, 7-day treatment, or 14-day treatment on 30-day clinical failure rate in patients with uncomplicated gram-negative bacteremia: a randomized clinical trial. JAMA. 2020;323(21):2160-2169

3Molina J, Montero-Mateos E, Praena-Segovia J, et al. Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial. Clin Microbiol Infect. 2022;28(4):550-557

4Sutton JD, Stevens JW, Chang NN, et al. Oral β-lactam antibiotics vs fluoroquinolones or trimethoprim-sulfamethoxazole for definitive treatment of Enterobacterales bacteremia from a urine source. JAMA Netw Open. 2020;3(10):e2020166

5Punjabi C, Tien V, Meng L, Deresinski S, Holubar M. Oral fluoroquinolone or trimethoprim-sulfamethoxazole vs. β-lactams as step-down therapy for Enterobacteriaceae bacteremia: systematic review and meta-analysis. Open Forum Infect Dis. 2019;6(10):ofz364

6Tamma PD, Conley AT, Cosgrove SE, et al. Association of 30-day mortality with oral step-down vs continued intravenous therapy in patients hospitalized with Enterobacteriaceae bacteremia. JAMA Intern Med. 2019;179(3):316-323

7Heil EL, Bork JT, Abbo LM, et al. Optimizing the management of uncomplicated gram-negative bloodstream infections: consensus guidance using a modified Delphi process. Open Forum Infect Dis. 2021;8(10):ofab434

8Mponponsuo K, Brown KA, Fridman DJ, et al. Highly versus less bioavailable oral antibiotics in the treatment of gram-negative bloodstream infections: a propensity-matched cohort analysis. Clin Microbiol Infect. 2023;29(4):490-497

9Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. IDSA guidance on the treatment of antimicrobial-resistant gram-negative infections: version 1.0. Infectious Diseases Society of America; 2022. Available at: www.idsociety.org/practice-guideline/amr-guidance/

10Woods CR, Bradley JS, Chatterjee A, et al. Clinical practice guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2021 Guideline on diagnosis and management of acute hematogenous osteomyelitis in pediatrics. DOI: https://doi.org/10.1093/jpids/piab027

11Woods CR, Bradley JS, Chatterjee A, et al. Clinical practice guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2023 guideline on diagnosis and management of acute bacterial arthritis in pediatrics. J Pediatr Infect Dis Soc. Published online November 6, 2023. DOI: https://doi.org/10.1093/jpids/piad089

12Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54(8):e72-e112. DOI: https://doi.org/10.1093/cid/cis370

13Wald ER, Applegate KE, Bordley C, et al. Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years. Pediatrics. 2013;132(1):e262-e280. DOI: https://doi.org/10.1542/peds.2013-1071

14Lieberthal AS, Carroll AE, Chonmaitree T, et al. Clinical practice guideline: diagnosis and management of acute otitis media. Pediatrics. 2013;131(3):e964-e999. DOI: https://doi.org/10.1542/peds.2013-3791

15Rosenfeld RM, Shin JJ, Schwartz SR, et al. Clinical practice guideline: otitis media with effusion (update). Otolaryngol Head Neck Surg. 2016;154(1 Suppl):S1-S41. DOI: https://doi.org/10.1177/0194599815623467

16Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group a streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):e86-e102. DOI: https://doi.org/10.1093/cid/cis629

17Mattoo TK, Shaikh N, Nelson CP. Contemporary management of urinary tract infection in children. Pediatrics. 2021;147(2):e2020012138. DOI: https://doi.org/10.1542/peds.2020-012138

18Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. DOI: https://doi.org/10.1093/cid/ciq257

19Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt). 2017;18(1):1-76

20Puopolo KM, Lynfield R, Cummings JJ; American Academy of Pediatrics, Committee on Fetus and Newborn and Committee on Infectious Diseases. Management of infants at risk for group B streptococcal disease. Pediatrics. 2019;144(2):e20191881. DOI: https://doi.org/10.1542/peds.2019-2350

21Puopolo KM, Benitz WE, Zaoutis TE; American Academy of Pediatrics, Committee on Fetus and Newborn and Committee on Infectious Diseases. Management of neonates born at ≥35 0/7 weeks’ gestation with suspected or proven early onset bacterial sepsis. Pediatrics. 2018;142(6):e20182894. DOI: https://doi.org/10.1542/peds.2018-2894

22Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25–e76. DOI: https://doi.org/10.1093/cid/cir531

23Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10–e52. DOI: https://doi.org/10.1093/cid/ciu296

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