This chapter will review the practice guidelines by the Infectious Diseases Society of America (IDSA).
Note: Empiric antibiotics should be tailored based on local pathogen prevalence and antibiotic susceptibility, pathogen-specific risk factors, and previous pathogens and antibiotic exposure. Once final culture and susceptibility results become available, empiric antibiotics should be optimized according to the identified pathogen(s) and susceptibility.
Hospital-acquired and ventilator-associated pneumonia
- •
Definitions:
- •
Pneumonia: new lung infiltrate plus clinical evidence of infection such as new fever, purulent sputum, leukocytosis, and oxygen desaturation.
- •
Hospital-acquired pneumonia (HAP): a pneumonia developing ≥48 h after hospital admission.
- •
Ventilator-associated pneumonia (VAP): a pneumonia developing >48 h after endotracheal intubation.
- •
- •
Risk factors for multidrug-resistant (MDR) pathogens ( Box 11.1 )
- •
Pathogens in intensive care unit (ICU) patients:
- •
Methicillin-resistant Staphylococcus aureus (MRSA)
- •
Pseudomonas aeruginosa (PSA)
- •
Gram-negative bacilli
- •
- •
Treatment for HAP ( Table 11.1 )
- •
If NO risk for MDR pathogens: choose one agent from regimen A that has activity against PSA and methicillin-susceptible Staphylococcus aureus (MSSA)
- •
If MDR pathogens suspected: choose one agent each from regimen A and B with activity against PSA and one agent from regimen C with activity against MRSA
Table 11.1
DRUG
STANDARD DOSING (IV)
RENAL DOSING
DIALYSIS
COMMENTS
Regimen A: Antipseudomonal β-Lactam
Aztreonam (Azactam)
1 g, 2 g
2 g q8h
CrCl 10–30: 1 g q8h
CrCl <10: 500 mg q8h
HD: 2 g LD, then 500 mg q8h a
CRRT: 2 g q12h
Possible cross-sensitivity between aztreonam and ceftazidime (<5%); avoid aztreonam if history of life-threatening reaction or anaphylaxis to ceftazidime. Other cephalosporins do not have the same risk as ceftazidime. Aztreonam and ceftazidime should be combined with vancomycin/linezolid due to lack of or less activity against gram-positive bacteria
Ceftazidime (Fortaz)
500 mg, 1 g, 2 g
2 g q8h
CrCl 31–50: 2 g q12h
CrCl 16–30: 2 g q24h
CrCl ≤15: 1 g q24h
HD: 1 g q24h a
CRRT: 2 g q12h
Cefepime (Maxipime)
1 g, 2 g
2 g q8h
CrCl 30–60: 2 g q12h
CrCl <30: 2 g q24h
HD: 1 g q24h a
CRRT: 1 g q8h or 2 g q12h
Risk of seizures in renal insufficiency
Imipenem (Primaxin)
250 mg, 500 mg
500 mg q6h
CrCl 10–50: 500 mg q8–12h
CrCl <10: 250–500 mg q12h
HD: 250–500 mg q12h a
CRRT: 500 mg q6–8h
Consider reserving for risk of ESBL producing pathogens
Cross-sensitivity with PCN allergy
Consider decreasing dose in patients <70 kg to prevent seizures
Meropenem (Merrem)
500 mg, 1 g
1 g q8h
CrCl 26–50: 1–2 g q12h
CrCl 10–25: 0.5–1 g q12h
CrCl <10: 0.5–1 g q24h
HD: 500 mg q24h a
CRRT: 500 mg–1 g q8h
Consider reserving for risk of ESBL producing pathogens
Cross sensitivity w/ PCN allergy
Piperacillin-tazobactam (Zosyn)
2.25 g, 3.375 g, 4.5 g
4.5 g q6h
CrCl 20–40: 3.375 g q6h
CrCl <20: 2.25 g q6h
HD: 2.25 g q8h a
CRRT: 3.375 g q6h
Consider extended infusion for critically ill: 4.5 g ×1 over 30 min, followed 4 h later by 4 h infusion q8h
Regimen B: Antipseudomonal Non-β-Lactam
Amikacin
Standardized doses: 250–750 mg (round to nearest 50 mg)
CD: 5–7.5 mg/kg q8h
ODD: 15–20 mg/kg q24h
CrCl 20–60:
CD: 5–7.5 mg/kg q12–24h b
ODD: 15–20 mg/kg q36–48h
CrCl <20:
CD: 5 mg/kg LD then based on level
ODD not recommended
HD: 5 mg/kg a , b
CRRT: 10 mg/kg LD, then 7.5 mg/kg q24–48h b
Consult Pharmacist for dosing
Goal level (mcg/mL):
Amikacin: peak: 25–35; trough: ≤8
Gentamicin/tobramycin: peak: 6–8; trough: ≤1–2
Goal for ODD: refer to Hartford nomogram ( Fig. 10.1 )
Use ideal or adjusted BW for obese
ADR: nephrotoxicity and ototoxicity
Gentamicin/Tobramycin
Standardized doses: 60–120 mg (round to nearest 10 mg)
CD: 1–2.5 mg/kg q8–12h
ODD: 5–7 mg/kg q24h
CrCl 20–60:
CD: 1–2.5 mg/kg q12–24h b
ODD: 5–7 mg/kg q36–48h
CrCl <20:
CD: 1–2.5 mg/kg LD, then based on level
ODD not recommended
HD: 1.5–2 mg/kg a , b
CRRT: 1.5–2 mg/kg q24–48h b
“
Ciprofloxacin (Cipro)
200 mg, 400 mg
400 mg q8h
CrCl 5–29: 400 mg q24h
HD: 400 mg q24h a
CRRT: 400 mg q12–24h
CI: myasthenia gravis, children due to musculoskeletal toxicity. ADR: tendonitis/tendon rupture, photosensitivity, peripheral neuropathy, CNS effects, hepatotoxicity, crystalluria, QT prolongation
Levofloxacin (Levaquin)
250 mg, 500 mg, 750 mg
750 mg daily
CrCl 20–49: 750 mg q48h
CrCl 10–19: 750 mg ×1 then 500 mg q48h
HD: 750 mg ×1 then 500 mg q48h a
CRRT: 750 mg ×1 then 250 mg q24h
“
Colistin (Coly-Mycin M)
150 mg
300 mg CBA ×1 then 150 mg CBA q12h
CrCl 20–50: 300 mg CBA ×1 then 150 mg CBA q24h
CrCl <20: 300 mg CBA ×1 then 150 mg CBA q48h
HD: 1.5 mg CBA/kg q24–48h a
ADR: nephrotoxicity
Reserve for carbapenemase-producing GNB
IV colistin does not achieve adequate concentrations in the lung; consider concurrent inhaled colistin (150 mg CBA q8h over 60 min) for carbapenemase producers
Polymyxin B
50 mg
2.5 mg/kg ×1 then 1.25–1.5 mg/kg q12h
CrCl 30–80: 2.5 mg/kg ×1 then 1–1.5 mg/kg q24h
CrCl <30: 2.5 mg/kg ×1 then 1–1.5 mg/kg q2–3d
Anuric: 2.5 mg/kg ×1 then 1 mg/kg q5–7d
HD: 25 mg IM q24h
10,000 units = 1 mg
ADR: nephrotoxicity
Reserve for carbapenemase-producing GNB
Regimen C for MRSA
Vancomycin (Vancocin)
Standardized doses: 0.5–2 g (round to nearest 250 mg)
15–20 mg/kg q8–12h
Consider 25–30 mg/kg LD
Max: 2 g/dose
CrCl 15–50: 750–1500 mg q24h
CrCl <15: 750–1500 mg b
HD: 500–1000 mg a , b
CRRT: 15–25 mg/kg LD, then 1 g q24–48h b
Consult pharmacist for dosing
Goal trough: 15–20 mcg/mL
Use actual BW
Linezolid (Zyvox)
600 mg
600 mg q12h a
No change
No change
DDI: discontinue SSRI 2 weeks before linezolid to reduce risk of serotonin syndrome and/or toxicity
Telavancin (Vibativ)
750 mg
10 mg/kg q24h
CrCl 30–50: 7.5 mg/kg q24h
CrCl 10–29: 10 mg/kg q48h
CrCl <10: not studied
HD/CRRT: not studied
FDA approval for HAP/VAP caused by Staphylococcus aureus only
Reserve for failure/intolerance to vancomycin/linezolid
New Antimicrobial
Ceftolozane 1 g-tazobactam 0.5 g (Zerbaxa 1.5 g)
3 g q8h
CrCl 30–50: 1.5 g q8h
CrCl 15–29: 750 mg q8h
CrCl <15 not on HD: not studied
ESRD on HD: 2.25 g ×1 then 450 mg q8h a
Reserve for MDR Pseudomonas aeruginosa
Notes:
- •
If aztreonam replaced by a β-lactam for penicillin allergy, include coverage for MSSA
- •
For HAP and VAP, a 7-day antibiotic therapy is recommended
- •
Fluoroquinolones and broad-spectrum cephalosporins have highest risk of C. difficile infection
- •
Vancomycin and piperacillin-tazobactam combination has been associated with acute kidney injury
- •
Daptomycin should not be used for HAP/VAP due to inactivation by surfactant and inadequate concentrations in the respiratory track
- •
Ceftaroline has activity against MRSA, however, only approved by FDA for CAP caused by MSSA or Streptococcus pneumoniae
- •
Tigecycline has activity against MRSA, however, only approved by FDA for CAP caused by Streptococcus pneumoniae; meta-analysis of Phase 3 and 4 trials demonstrated higher risk of mortality in tigecycline treated patients with VAP
- •
Among carbapenems, doripenem is not approved by FDA for pneumonia and should not be used
- •
- •
Treatment for VAP: same therapy as HAP with risk for MDR
Community-associated pneumonia
- •
Definition: IDSA defines pneumonia as new lung infiltrate plus clinical evidence of infection such as new fever, purulent sputum, leukocytosis, and oxygen desaturation.
- •
Risk factors for drug-resistant pathogens:
- •
Previous antibiotic therapy
- •
Recent hospitalization
- •
Immunosuppression
- •
Pulmonary comorbidity (cystic fibrosis, bronchiectasis, frequent glucocorticoid/antibiotic use in chronic obstructive pulmonary disease)
- •
Aspiration
- •
Medical comorbidities (diabetes, alcoholism)
- •
- •
Pathogens in ICU patients:
- •
Streptococcus pneumoniae (most common)
- •
Staphylococcus aureus
- •
Legionella species
- •
Gram-negative bacilli
- •
Haemophilus influenzae
- •
- •
Treatment ( Table 11.2 )
- •
If NO risk for PSA or MRSA: β-lactam plus azithromycin or levofloxacin or moxifloxacin
- •
If PSA suspected: antipneumococcal, antipseudomonal β-lactam + one of the following
- •
Ciprofloxacin or levofloxacin
- •
Aminoglycoside + azithromycin
- •
Aminoglycoside + levofloxacin or moxifloxacin
- •
- •
If community-acquired MRSA suspected: add vancomycin or linezolid
- •
If penicillin allergy: replace a β-lactam with aztreonam and a respiratory fluoroquinolone
Table 11.2
DRUG
STANDARD DOSING (IV)
RENAL DOSING
DIALYSIS
COMMENTS
β-Lactams
Cefotaxime (Claforan)
1 g, 2 g
1–2 g q8h
CrCl <20: 50% dose q8h
HD: 1–2 g q24h a
CRRT: 1–2 g q8h
10% cross-sensitivity with PCN allergy
Ceftaroline (Teflaro)
400 mg, 600 mg
600 mg q12h
CrCl 31–50: 400 mg q12h
CrCl 15–30: 300 mg q12h
CrCl <15: 200 mg q12h
HD: 200 mg q12h a
CRRT: 200 mg q12h
“
Ceftriaxone (Rocephin)
1 g, 2 g
1–2 g daily a
No change
No change
“
Ampicillin-sulbactam (Unasyn)
1.5 g, 3 g
3 g q6h
CrCl 15–29: 3 g q12h
CrCl <15: 3 g q24h
HD: 3 g q12–24h a
CRRT: 3 g q8h
—
Ertapenem (Invanz)
1 g
1 g daily
CrCl ≤30: 500 mg daily
HD: 500 mg daily a
Cross-sensitivity with PCN allergy
Azithromycin and Quinolones
Azithromycin (Zithromax)
500 mg
500 mg daily
No change
No change
ADR: QT prolongation, hepatotoxicity
Ciprofloxacin (Cipro)
200 mg, 400 mg
400 mg q8h
CrCl 5–29: 400 mg q24h
HD: 400 mg q24h a
CRRT: 400 mg q12–24h
CI: myasthenia gravis, children due to musculoskeletal toxicity. ADR: tendonitis/tendon rupture, peripheral neuropathy, CNS effects, photosensitivity, hepatooxicity, crystalluria, QT prolongation
Levofloxacin (Levaquin)
250 mg, 500 mg, 750 mg
750 mg daily
CrCl 20–49: 750 mg q48h
CrCl 10–19: 750 mg ×1 then 500 mg q48h
HD: 750 mg ×1 then 500 mg q48h a
CRRT: 750 mg ×1 then 250 mg q24h
“
Moxifloxacin (Avelox)
400 mg
400 mg daily
No change
No change
“
Antipneumococcal, Antipseudomonal β-Lactams
Piperacillin-tazobactam (Zosyn)
2.25 g, 3.375 g, 4.5 g
4.5 g q6h
CrCl 20–40: 3.375 g q6h
CrCl <20: 2.25 g q6h
HD: 2.25 g q8h a
CRRT: 3.375 g q6h
Off-label extended infusion: 3.375–4.5 g ×1 over 30 min, followed 4 h later by 4 h infusion q8h
Cefepime (Maxipime)
1 g, 2 g
2 g q8h
CrCl 30–60: 2 g q12h
CrCl <30: 2 g q24h
HD: 1 g q24h a
CRRT: 1 g q8h or 2 g q12h
Risk of seizures in renal insufficiency
Ceftazidime (Fortaz)
500 mg, 1 g, 2 g
2 g q8h
CrCl 31–50: 2 g q12h
CrCl 16–30: 2 g q24h
CrCl ≤15: 1 g q24h
HD: 1 g q24h a
CRRT: 2 g q12h
Possible cross-sensitivity between aztreonam and ceftazidime (<5%): see Table 11.1 for detail
Imipenem (Primaxin)
250 mg, 500 mg
500 mg q6h
CrCl 10–50: 500 mg q8–12h
CrCl <10: 250–500 mg q12h
HD: 250–500 mg q12h a
CRRT: 500 mg q6–8h
Cross-sensitivity with PCN allergy. Consider decreasing dose in patients <70 kg to prevent seizures
Meropenem (Merrem)
500 mg, 1 g
1 g q8h
CrCl 26–50: 1–2 g q12h
CrCl 10–25: 500 mg–1 g q12h
CrCl <10: 500 mg–1 g q24h
HD: 500 mg q24h a
CRRT: 500 mg–1 g q8h
Cross-sensitivity with PCN allergy
Aminoglycosides
Amikacin
Standardized doses: 250–750 mg (round to nearest 50 mg)
CD: 5–7.5 mg/kg q8h
ODD: 15–20 mg/kg q24h
CrCl 20–60:
CD: 5–7.5 mg/kg q12–24h b
ODD: 15–20 mg/kg q36–48h
CrCl <20:
CD: 5 mg/kg load then based on level
ODD not recommended
HD: 5 mg/kg a , b
CRRT: 10 mg/kg LD, then 7.5 mg/kg q24–48h b
Consult pharmacist for dosing
Goal level (mcg/mL):
Amikacin: peak: 25–35; trough: ≤8
Gentamicin/tobramycin: peak: 6–8; trough: ≤1–2
Goal for ODD: refer to Hartford nomogram ( Fig. 10.1 )
Use ideal or adjusted BW for obese
ADR: nephrotoxicity and ototoxicity
Gentamicin/Tobramycin
Standardized doses: 60–120 mg (round to nearest 10 mg)
CD: 1–2.5 mg/kg q8–12h
ODD: 5–7 mg/kg q24h
CrCl 20–60:
CD: 1–2.5 mg/kg q12–24h b
ODD: 5–7 mg/kg q36–48h
CrCl <20:
CD: 1–2.5 mg/kg load, then based on level
ODD not recommended
HD: 1.5–2 mg/kg a , b
CRRT: 1.5–2 mg/kg q24–48h b
“
Antibiotics for CA-MRSA
Vancomycin (Vancocin)
Standardized doses: 0.5–2 g (round to nearest 250 mg)
15–20 mg/kg q8–12h
Consider 25–30 mg/kg LD
Max: 2 g/dose
CrCl 15–50: 750–1500 mg q24h
CrCl <15: 750–1500 mg b
HD: 500–1000 mg a , b
CRRT: 15–25 mg/kg load, then 1 g q24–48h b
Consult pharmacist for dosing
Goal trough: 15–20 mcg/mL
Use actual BW
Linezolid (Zyvox)
600 mg
600 mg q12h
No change
No change
Give post HD on HD days
DDI: discontinue SSRI 2 weeks before linezolid to reduce risk of serotonin syndrome or toxicity
Monobactam for Penicillin-Allergy
Aztreonam (Azactam)
1 g, 2 g
2 g q8h
CrCl 10–30: 1 g q8h
CrCl <10: 500 mg q8h
HD: 2 g LD, then 500 mg q8h a
CRRT: 2 g q12h
If life-threatening or anaphylactic reaction to penicillin/cephalosporins, replace aztreonam with levofloxacin+ AG
New Antimicrobials
Omadacycline (Nuzyra)
100 mg IV
150 mg PO
200 mg IV ×1 then 100 mg IV or 300 mg PO q24h
No change
No change
Broad spectrum of activity against atypical CAP pathogens, MRSA, many GNR, and anaerobes, but NO coverage against PSA
Delafloxacin (Baxdela)
Activity against MRSA and PSA, but not FDA approved for the treatment of respiratory tract infections
Lefamulin
Pending FDA approval: a semisynthetic pleuromutilin antibiotic with narrow spectrum of activity against MRSA, Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis , and atypical CAP pathogens
Notes:
- •
Minimum 5 days is the recommended duration with those who have resolution of symptoms
- •
A longer duration of treatment may be necessary if empiric therapy was not active against the identified pathogen or if concomitant extrapulmonary infection such as meningitis or endocarditis
- •
For patients with QT prolongation, doxycycline may replace macrolides and fluoroquinolones
- •
Vancomycin and piperacillin-tazobactam combination has been associated with acute kidney injury
- •
Influenza
- •
Definition: IDSA defines influenza as an acute respiratory illness caused by seasonal influenza A or B viruses.
- •
Risk factors for complications from influenza:
- •
Age <5 years and ≥65 years
- •
Chronic pulmonary, cardiovascular, renal, hepatic, hematologic, or metabolic disorders or neurologic and neurodevelopment conditions
- •
Immunosuppression
- •
Pregnancy or 2 weeks postpartum
- •
Children ≤18 years on long-term aspirin
- •
American Indians/Alaska Natives
- •
Obesity (body mass index ≥40 kg/m 2 )
- •
Residents of nursing homes and long-term care facilities
- •
- •
Pharmacologic management of influenza ( Table 11.3 )
Table 11.3
DRUG
INFLUENZA ACTIVITY
STANDARD DOSING
RENAL DOSING
COMMENTS
Selective Inhibitor of Influenza Cap-Dependent Endonuclease
Baloxavir (Xofluza)
A and B
Treatment (PO): a single dose within 48 h of influenza symptoms
40–79 kg: 40 mg
≥80 kg: 80 mg
No change
New agent
ADR: diarrhea, nasopharyngitis
Neuraminidase Inhibitors: Drug of Choice
Oseltamivir (Tamiflu)
A and B
Treatment (PO/NG): 75 mg BID ×5 days
150 mg BID has been used for severe influenza
Prophylaxis (PO/NG): 75 mg daily
CrCl 30–60: 30 mg BID
CrCl 10–30: 30 mg daily
HD: 30 mg ×1 then 30 mg after every HD ×5 days a
CRRT: 30 mg daily ×5 days or 75 mg q48h ×5 days
ADR: headache, nausea, vomiting, delirium
Preferred in severe influenza
Consider longer duration of therapy for who remain severely ill after 5 days of therapy
Peramivir (Rapivab)
A and B; limited coverage for B
Treatment (IV):
Uncomplicated: 600 mg ×1
Complicated: 600 mg daily ×5–10 days if hospitalized, high risk
Uncomplicated:
CrCl 30–49: 200 mg ×1
CrCl <30: 100 mg ×1
Complicated:
CrCl 31–49: 150 mg daily
CrCl 10–30: 100 mg daily
CrCl <10: 100 mg ×1 then 15 mg daily
ESRD on HD: 100 mg ×1 then 100 mg 2 h after HD
ADR: diarrhea, neutropenia, hypersensitivity reactions, delirium
Zanamivir (Relenza)
A and B
Treatment (oral inh): two inhalations (10 mg) BID ×5 days
Prophylaxis (oral inh): two inhalations (10 mg) daily
No change
ADR: allergic reactions, nausea, diarrhea, headache, decline in respiratory function in patients with asthma/COPD, dizziness, bronchospasm
Avoid in chronic lung disease or severe influenza
Incompatible with mechanical ventilator circuit
Adamantanes: Not Recommended Due to High Resistance to Influenza A
Amantadine (Symmetrel)
A only
Treatment/prophylaxis: 200 mg daily or 100 mg BID
CrCl 30–50: 200 mg ×1 then 100 mg daily
CrCl 15–29: 200 mg ×1 then 100 mg QOD
CrCl <15 and HD: 200 mg q7d
CRRT: 100 mg daily or QOD
ADR: presyncope/syncope, orthostatic hypotension, falling, peripheral edema, illusion, dizziness, delusions, lower seizure threshold, insomnia, hallucination, paranoia, anticholinergic effects
Rimantadine (Flumadine)
A only
Treatment/prophylaxis: 100 mg BID ×5–7 days
CrCl <30: 100 mg daily
ADR: anticholinergic effects, dizziness, vomiting, nausea
Notes:
- •
If indicated, initiate antiviral therapy promptly; most effective if started within 48 h of symptom onset
- •
Treatment not recommended for uncomplicated influenza presenting >48 h of symptoms onset
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