Other infections





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 )



    Box 11.1

    Risk Factors for Multidrug-Resistant Pathogens




    From Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis . 2016;63(5):e61–e111.










    HAP VAP



    • Previous IV antibiotic therapy within 90 days




    • Previous IV antibiotic therapy within 90 days



    • Septic shock at VAP onset



    • ARDS preceding VAP



    • ≥5 days of hospitalization prior to VAP



    • Acute renal replacement therapy prior to VAP


    ARDS , Acute respiratory distress syndrome; HAP , Hospital-acquired pneumonia; IV , intravenously; VAP , Ventilator-associated pneumonia




  • 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

    Empiric Antimicrobial Therapy for HAP/VAP in ICU

    Data from Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis . 2016;63(5):e61–e111.



















































































































    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 )




      Figure 11.1


      Management of Skin and Soft tissue Infections (SSTIs).

      C & S, Culture and sensitivity; I & D, Incision and drainage; MRSA , Methicillin-resistant Staphylococcus aureus; MSSA , Methicillin-sensitive Staphylococcus aureus; Rx , Treatment; TMP/SMX , Trimethoprim-sulfamethoxazole.

      From Stevens DL, Bisno AL, Chambers HF, et al . Infectious Diseases Society of America . 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.



    • 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


    ADR , Adverse drug reaction; BW , Body weight; CAP , Community-acquired pneumonia; CBA , Colistin base activity; CD , Conventional dosing; CI , Contraindication; CNS , Central nervous system; CrCl , Creatinine clearance; CRRT , Continuous renal replacement therapy; DDI , Drug-drug interaction; ESBL , Extended-spectrum β-lactamase; ESRD , End-stage renal disease; FDA , Food and Drug Administration; GNB , Gram-negative bacilli; HAP , Hospital-acquired pneumonia; HD , Hemodialysis; ICU , Intensive care unit; IM , Intramuscularly; IV , Intravenously; LD , Losing dose; MDR , Multidrug resistant; MRSA , Methicillin-resistant Staphylococcus aureus; MSSA , Methicillin-susceptible Staphylococcus aureus; ODD , Once-daily dosing; PCN , penicillin; SSRI , Selective serotonin-reuptake inhibitor; VAP , Ventilator-associated pneumonia

    Drugs without brand names are denoted by generic name only

    a Give post HD on HD days


    b Based on level




  • 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

    Empiric Antimicrobial Therapy for CAP in ICU

    Data from Mandell LA, Wunderink RG, Anzueto A, et al.; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(S2):S27–S72.
























































































































































    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


    ADR , Adverse drug reaction; AG , Aminoglycoside; BW , Body weight; CA , Community acquired; CAP , Community-acquired pneumonia; CI , Contraindication; CNS , Central nervous System; CD , Conventional dosing; CrCl , Creatinine clearance; CRRT , Continuous renal replacement therapy; DDI , Drug-drug interaction; FDA , Food and drug administration; GNR , gram-negative rods; HD , Hemodialysis; ICU , Intensive care unit; IV , Intravenously; LD , Loading dose; MRSA , Methicillin-resistant Staphylococcus aureus ; ODD , Once daily dosing; PCN , Penicillin; PO , Take orally; PSA , Pseudomonas aeruginosa ; SSRI , Selective serotonin-reuptake inhibitors

    a Give post HD on HD days


    b Based on level




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

    Influenza-Specific Pharmacotherapy

    Data from Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 Update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenzaa. Clin Infect Dis. 2018 ; 68(6):e1-47.






















































    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


    ADR , Adverse drug reaction; BID , Twice daily; COPD , Chronic obstructive pulmonary disease; ESRD , End-stage renal disease; HD , Hemodialysis; inh , Inhalation; IV , Intravenously; NG, Via nasogastric tube; PO , Orally; QOD , Every other day

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