Rational use of antibiotics (PowerPoint)

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					Rational use of antibiotics

   Dr. Sanjana Tarannum
       Intern, MU X
 Definition
  Antibiotics are substances that kill or inhibit the growth of micro-
  Bacteriostatic (Tetracycline, Chloramphenicol)
  Bactericidal (Beta lactams, Aminoglycosides)

 Misuse of Antibiotics:
  Overuse and inappropriate use of antibiotics has fueled a major
  increase in prevalence of multidrug -resistant pathogens leading
  some to speculate that we are nearing the end of antibiotic era.
  Development of novel drugs has slowed unfortunately. It seems
  likely that over the next decade we will have to rely on currently
  available families of drugs. So, it is extremely important that we
  prescribe antibiotics rationally in appropriate dosage and in
  appropriate routes.
Classification of antibiotics
Based on their mechanism of action, antibiotics
   can be divided into the following classes:

   Inhibitors of Cell Wall synthesis
   Inhibitors of Protein synthesis
   Inhibitors of Nucleic Acid synthesis
Inhibitors of Cell Wall Synthesis
This class includes:
 Penicillins
 Cephalosporins
 Carbapenems
 Monobactams
 Vancomycin
 Beta lactamase
Beta Lactams
 Penicillins:
a.   Narrow spectrum (natural) : benzylpenicillin,
b.   Antistaphylococcal: Cloxacillin, flucloxacillin
c.   Broad spectrum: Ampicillin, amoxicillin
d.   Mecillinam: pivmecillinam
e.   Monobactam: Aztreonam
f.   Antipseudomonal: Piperacillin, ticarcillin
g.   Carbapenems: Meropenem, Imipenem-cilastatin
h.   Penicillin-beta lactamase inhibitor combinations: co-amoxiclav,
Spectrum of action of Penicillins
 Natural Penicillin (narrow    Amoxicillin (broad
   spectrum)                     spectrum)
Class              Examples      Routes of
First generation   Cefalexin     Oral
                   Cefazolin     i.v.
Second             Cefuroxime    Oral/ i.v.
generation         Cefoxitin
Third generation   Cefixime      Oral
                   Ceftriaxone   i.v.
                   Ceftazidime   i.v.
Fourth             Cefipime      i.v.
Spectrum of action of Cephalosporins
 Cefuroxime (2nd    Ceftazidime (3rd
  generation)         generation)
Pharmacokinetics and Adverse Effects
of Beta lactams
 Pharmacokinetics:                 Adverse Effects:
•   Not inhibited by abscess        Allergic reactions: itch, rash,
    environment (low pH,PMNs)        fever, angioedema, rarely
•   Low CSF levels except in         anaphylactic reaction
    presence of inflammation        GI upset and diarrhoea
•   Safe in pregnancy               Direct intrathecal injection of
•   Dosage needs to be               a beta lactam is
    reduced in cases of              contraindicated ( very high
    impaired renal function          doses cause seizures and
•   Delayed excretion with           encephalopathy)
    concurrent administration of    Interstitial nephritis and
    probenecid                       increased renal damage in
•   Synergistic effect with          combination with
    aminoglycosides                  aminoglycosides
Inhibitors of Protein Synthesis
This class includes:

 Macrolides- erythromycin, clarithromycin,
   Lincosamides- clindamycin
   Aminoglycosides- gentamicin, tobramycin,
    amikacin, netilmicin,neomycin,
   Tetracyclines- tetracycline, doxycycline,minocycline
   Chloramphenicol
Mechanism and Spectrum of Action of
 It binds to the 50S subunit of ribosome and blocks the
   translocation and formation of initiation complex, thereby
   inhibiting protein synthesis.
Pharmacokinetics and Adverse Effects
of Macrolides
 Pharmacokinetics:          Adverse Effects

• Poorly absorbed orally    • GI upset
                            • Cholestatic jaundice
• Short half life (except
  azithromycin)             • Prolongation of QT
                              interval (erythromycin)
• Bacteriostatic
                            • Diarrhoea related to Cl.
• Good CSF penetration        Difficile
  (erythromycin)            • Theophylline, oral
• Dose adjustment for         anticoagulants cannot
  renal failure is not        be administered
  necessary                   simultaneously
Mechanism and Spectrum of action of
Pharmacokinetics and Adverse Effects
of Aminoglycosides
 Pharmacokinetics          Adverse Effects

• Negligible oral          •   Ototoxic (permanent)
                           •   Nephrotoxic (
• Negligible CSF and
  corneal penetration          reversible): not to be
                               given with loop
• Dose adjustment is
  critical in renal            diuretics,
  impairment                   vancomycin,
• Post antibiotic effect
  allows daily once        •   Neuromuscular
  dosing                       blockade after rapid i.v.
Mechanism and Spectrum of action of
 Spectrum of Action of        Mechanism of Action:
  Tetracyclines have a
  broad spectrum of
  activity; mostly used
  against Mycoplasma,
  Chlamydia and
  Rickettsia, plus Borrelia
  and other spirochaetes.
Pharmacokinetics and Adverse Effects
of Tetracyclines
 Pharmacokinetics           Adverse Effects

                            •   Contraindicated in renal
• Bacteriostatic                failure (except doxycycline
• Best oral absorption in       and minocycline)
  fasting state             •   Nausea, diarrhoea
• CSF level increases in    •   Binds to metallic ions in
                                bones and teeth (to be
  chronic inflammation          avoided in children and in
                            •   Phototoxic skin reactions
                            •   Hypernatremia
Inhibitors of Nucleic Acid synthesis
This group includes:
 Sulphonamides: Sulfamethoxazole, sulfadoxine
 Trimethoprim
 Quinolones: Ciprofloxacin, levofloxacin, pefloxacin,
  ofloxacin, norfloxacin, gatifloxacin, moxifloxacin,
 Rifampicin
 Azoles: This group includes-
• Antibacterial- Metronidazole, secnidazole, tinidazole,
• Antifungal- Ketoconazole, fluconazole, Isoconazole,
  Itraconazole, Clotrimazole
• Antihelminth- Albendazole, Mebendazole,
Mechanism of action of
Sulphonamides and Trimethoprim
Pharmacokinetics and Adverse Effects
of Sulphonamides and Trimethoprim
 Pharmacokinetics             Adverse Effects

• Well absorbed orally        • Fatal marrow dysplasia
  with good bioavailability     and haemolysis in
• Sulphonamides are well        G6PD deficiency
  distributed in ECF
                              • Skin and
• Trimethoprim is               mucocutaneous
  lipophilic with high
                                reactions: Stevens-
  tissue concentrations
                                Johnson syndrome
• Dose reduction
  necessary in renal          • Contraindicated in
  failure                       pregnancy
Mechanism of Action of Quinolones
Spectrum of Action of Quinolones
Pharmacokinetics and Adverse Effects
of Quinolones
 Pharmacokinetics                  Adverse Effects

•   Well absorbed after oral       •   GI side effects
    administration but delayed     •   CNS effects such as
    by food, antacids, ferrous         confusion and seizures in
    sulphate and multivitamins.        the elderly
•   Wide volume of distribution.   •   Rare skin reactions
•   Dose adjustment required       •   Should be avoided in
    in renal impairment                pregnancy
    (except moxifloxacin and       •   Not routinely
    trovafloxacin)                     recommended for use in
•   These two drugs are                patients under 18 years of
    contraindicated in hepatic         age
Mechanism and Spectrum of Action of
Azoles (antibacterial)
 Spectrum of action:
  It is bacteriostatic. It
  acts mainly against
  anaerobic bacteria and
  retains significant
  antiprotozoal activity.
Mechanism of action of Azoles
Pharmacokinetics and Adverse Effects
of Azoles
 Pharmacokinetics        Adverse Effects
• Almost completely
  absorbed after oral    •   Metallic taste
  administration (60%    •   Severe vomiting if taken with
  after rectal               alcohol
• Well distributed,
  especially brain and
• Safe in pregnancy.
Classification on the basis of the
 Antivirals
 Antibacterials
 Antifungals
 Antiparasites:
Common viral diseases
 CNS-Viral meningitis, viral encephalitis
 Childhood exanthems- Measles, Mumps,
  Rubella, Chicken pox etc.
 Systemic- Infectious mononucleosis,
  Influenza, CMV, Dengue, viral haemorrhagic
  fevers etc.
 GIT & HBS- Rotavirus; Viral hepatitis
 Respiratory- Adenovirus
Viral Encephalitis
 Aetiology: HSV, Arbovirus, Japanese B

 Management:
  In case of HSV: Aciclovir 10mg/kg i.v. 8
  hourly for 2-3 weeks (early to all patients
  suspected of suffering from viral
  Initiation of treatment should not await
  microbiological diagnosis.
Viral Hepatitis
    Aetiology:
a.   Commonly :Hepatotrophic viruses e.g. Hepatitis A,B,C,D,E
b.   Less commonly: CMV, EBV
c.   Rarely: HSV, Yellow fever virus
    Management:
•    No antivirals required for Hep A and E, acute Hep B infection
•    In chronic Hep B infection : Options are-
     Interferon- Low viral load, serum transaminases>twice normal,
     Lamivudine- Decompensated cirrhosis.
     Adefovir- C/I- Renal failure
•    Chronic Hep C infection : Pegylated alpha interferon weekly
     s/c + oral ribavirin
Common Bacterial diseases
 CNS: Meningitis, brain abscess etc
 Respiratory: URTI, Pneumonia, Lung abscess,
   CVS: Acute rheumatic fever, Infective endocarditis
   GIT and HBS: Cholera, Bacillary dysentery, Enteric
    fever, gastroenteritis, peritonitis,liver abscess
   Genitourinary: UTI, pyelonephritis, STDs
   Musculoskeletal: Osteomyelitis, Septic arthritis
   Mycobacterial Infections: Tuberculosis, Leprosy
   Rickettsial Infections
   Chlamydial Infections
   Systemic Infections: Sepsis syndrome
Pyogenic Meningitis (Cause Known)
Age of       Neonate         Preschool          Older child and adult
onset                        child

Common       Gram            Haemophilus        1. Neisseria meningitidis
             Negative        influenzae         2. Streptococcus pneumoniae
Regimen of                   Cefotaxime 2 g     1.Benzylpenicillin 2.4 g i.v. 4-
choice                       i.v. 6-hourly or   hourly for 5-7 days
                             ceftriaxone 2 g    2. Cefotaxime 2 g i.v. 6-hourly
                             i.v. 12-hourly     or
                             for 10-14 days     ceftriaxone 2 g i.v. 12-hourly
                                                for 10-14 days
                                                add vancomycin 1 g i.v. 12-
                                                hourly or rifampicin 600 mg
                                                i.v. 12-hourly(in beta lactam
                                                resistant groups)
Pyogenic Meningitis (Cause
1. Patients with typical              Benzylpenicillin 2.4g i.v. 6 hourly
meningococcal rash
2. Adults (18-50) without a typical   Cefotaxime 2 g i.v. 6-hourly or
meningococcal rash                    Ceftriaxone 2 g i.v. 12-hourly

3. Suspicion of penicillin-           As above plus-
resistant pneumococcal infection      Vancomycin 1 g i.v. 12-hourly or
                                      Rifampicin 600 mg i.v. 12-hourly

4. Adults>50 years with suspected     As above plus-
L.monocytogenes infection             Ampicillin 2 g i.v. 4-hourly or
                                      Co-trimoxazole 50 mg/kg i.v.daily in two
                                      divided doses
5. Patients with anaphylaxis to beta Chloramphenicol 25 mg/kg i.v. 6-hourly
lactams                              plus
                                     Vancomycin 1 g i.v. 12-hourly
  Pneumonia- Community Acquired
Common organisms                       Uncommon organisms

S. pneumoniae, C. pneumoniae, M.       H.Influenzae, S.Aureus, Chlamydia
pneumoniae, L. Pneumophilia            psittaci,Coxiella burnetti,

Severe CAP

Clarithromycin 500 mg 12-hourly i.v. or
Erythromycin 500 mg 6-hourly i.v. plus
Co-amoxiclav 1.2 g 8-hourly i.v. or
Ceftriaxone 1-2 g daily i.v. or
Cefuroxime 1.5 g 8-hourly i.v. or
Amoxicillin 1 g 6-hourly i.v. plus flucloxacillin 2 g 6-hourly i.v.
Pneumonia-Community Acquired
 Uncomplicated CAP
Amoxicillin 500 mg 8-hourly orally
If patient is allergic to penicillin
      Clarithromycin 500 mg 12-hourly orally or
      Erythromycin 500 mg 6-hourly orally
If Staphylococcus is cultured or suspected
      Flucloxacillin 1-2 g 6-hourly i.v. plus
      Clarithromycin 500 mg 12-hourly i.v.
If Mycoplasma or Legionella is suspected
      Clarithromycin 500 mg 12-hourly orally or i.v. or
      Erythromycin 500 mg 6-hourly orally or i.v. plus
      Rifampicin 600 mg 12-hourly i.v. in severe cases
Pneumonia-Hospital Acquired
 Hospital Acquired Pneumonia
•   Aetiology- Gram Negative bacteria
    e.g.Escherichia,Pseudomonas,Klebsiella and MRSA

•   Management-
        a third-generation cephalosporin (e.g. cefotaxime) plus an
    aminoglycoside (e.g. gentamicin) or
        meropenem or
        a monocyclic β-lactam (e.g. aztreonam) plus flucloxacillin.

 Aspiration Pneumonia
• Management-
         Co-amoxiclav 1.2g 8-hourly plus
         Metronidazole 500mg 8-hourly
Lung Abscess & Bronchiectasis
 Suppurative pneumonia and Lung abscess
Aetiology: Kleb. Pneumoniae, Strep. pneumoniae, Staph. aureus,
  Strep. pyogenes, H. influenzae and, in some cases, anaerobic

Management: Amoxicillin 500mg 8-hourly orally.
If anaerobic infection is suspected, oral metronidazole 400mg
    8hourly orally.
Treatment for 4-6 weeks in cases of lung abscess.

 Bronchiectasis
Antibiotic therapy should be guided by microbiological results.
  Frequently used are-
  oral ciprofloxacin (250-750 mg 12-hourly) or
  ceftazidime by intravenous injection or infusion (1-2 g 8-hourly).
 Category I                    Category II
Criteria: New smear positive   Criteria: sputum smear positive
   pulmonary TB, new smear        pulmonary TB with history of
   negative pulmonary TB,         treatment more than 1 month,
   extrapulmonary TB,             relapse, treatment failure,
   concomitant HIV/AIDS           treatment after default

Intensive phase:               Intensive phase:
(HRZE) for 2 months            2 months (HRZE)S/ 1 month (HRZE)
Continuation phase:            Continuation phase:
(HR) for 4 months              5 months (HR)E
Acute Rheumatic Fever
 Aetiology: Immunological response after infection by
  Group A Streptococci
 Management:
•  Acute attack-A single dose of benzyl penicillin 1.2 million U i.m.
   or oral phenoxymethylpenicillin 250 mg 6-hourly for 10 days.
• Secondary prevention-Benzyl penicillin 1.2 million U i.m.
   monthly (if compliance is in doubt) or
   oral phenoxymethylpenicillin 250 mg 12-hourly.
Treatment should be continued for 5 years or till age of the
   patient is 21 years (whichever is longer). In those with residual
   heart disease, prophylaxis should continue until 10 years after
   the last episode or 40 years of age, whichever is longer.
Infective Endocarditis
Acute- By Staph. aureus and coagulase negative staphylococci.
Benzylpenicillin (1.2 g 4 hourly) [penicillin sensitive]
Flucloxacillin (2g 4 hourly) [penicillin resistant,meticillin sensitive]
Vancomycin (1g 12 hourly) and gentamicin (1mg/kg 8 hourly)
     [penicillin and meticillin resistant]

Subacute- By viridans streptococci, enterococci, Gram negative
     bacilli (HACEK) group and anaerobes
Viridans streptococci: Benzylpenicillin and gentamicin
Ampicillin (2g 4 hourly) and gentamicin [ampicillin sensitive]
Vancomycin (1g 12 hourly) and gentamicin [ampicillin resistant]

Route of administration: Intravenous
Duration of treatment: 4 (native valves)- 6 (prosthetic valves) weeks
Gastrointestinal Infections
 Cholera:
  Tetracycline 250 mg 6-hourly for 3 days,
  Doxycycline 300 mg single dose or
  Ciprofloxacin 1 g in adults
 Bacillary Dysentery:
  Ciprofloxacin 500 mg 12-hourly for 3 days
 Helicobacter pylori Infection:
  Two antibiotics (from amoxicillin,
  clarithromycin and metronidazole) for 7 days
Enteric Fever
Aetiology: Salmonella typhi and Salmonella paratyphi
   A and B
Drugs of choice: Fluoroquinolones (Ciprofloxacin
   500 mg 12-hourly)
Alternatives: Extended-spectrum cephalosporins,
   ceftriaxone and cefotaxime
Fluoroquinolone resistance: Azithromycin 500 mg once
Treatment should be continued for 14 days.
Chronic carrier: Should be treated for 4 weeks with
Liver Abscess
 Aetiology (pyogenic): E.coli, various streptococci
  esp. Strep. Milleri; anaerobes like streptococcus and
  (amoebic): Entamoeba histolytica
 Management:
• Pyogenic: Combination of antibiotics e.g. ampicillin,
  gentamicin and metronidazole
• Amoebic: Metronidazole (800 mg 8-hourly for 5 days)
  or tinidazole (2 g daily for 3 days)
  Luminal amoebicide-diloxanide furoate (500 mg 8-
  hourly for 10 days)
Sepsis and Spontaneous bacterial
 Sepsis: Broad spectrum antibiotics covering
  both Gram positive and Gram negative
  organisms should be given after sending
  blood and other specimens for culture.
 Spontaneous bacterial peritonitis:
• In CLD with ascites: mostly caused by E.coli.
  Treatment should be with broad spectrum
  antibiotics e.g. cefotaxime.Recurrence may
  be reduced by quinolones e.g.norfloxacin or
UTI & Pyelonephritis
 Aetiology: E.coli, Proteus, Pseudomonas, streptococci,
  Staph. Epidermidis

 Choice of antibiotics: Trimethoprim, Nitrofurantoin,
  Ciprofloxacin, Norfloxacin, Co-amoxiclav,Cefuroxime, Cefalexin

 Duration of Treatment:
For UTI - 3days
For Pyelonephritis - 7-14 days
Severe cases require intravenous therapy, with a cephalosporin,
   quinolone or gentamicin
Type of           Monthly          Daily self-  Duration
Leprosy           supervised       administered of
                  drug             drug         treatment
                  treatment        treatment
Paucibacillary Rifampicin          Dapsone           6 months
                  600 mg           100 mg
Multibacillary    Rifampicin       Clofazimine       12 months
                  600 mg           50 mg
                  Clofazimine      Dapsone
                  300 mg           100 mg
 Paucibacillary single lesion is to be treated with a single
  dose of Ofloxacin 400 mg, Rifampicin 600 mg and Minocycline
  100 mg
STDs : Syphilis, Gonorrhoea,
Chlamydial infections
 Syphilis: Penicillin is the drug of choice. Doxycycline (in
  penicilin allergy) and azithromycin are also advocated.
 Chlamydia:
Azithromycin 1 g orally as a single dose or
Doxycycline 100 mg 12-hourly orally for 7 days
 Gonorrhoea:
Cefixime 400 mg stat or
Ciprofloxacin 500 mg orally stat or
Ofloxacin 400 mg orally stat or
Amoxicillin 3 g plus probenecid 1 g orally stat
Common fungal diseases
 Candidiasis                        Dermatophytes (ring
Caused by Candida albicans              worms):
                                    •  Microsporum
Treatment:                          •  Trichophyton
Systemic- Amphotericin B,           •  Epidermophyton
   Fluconazole, Voriconazole        Clinical forms include-
                                    Tinea corporis, tinea cruris,
Topical (oral or vaginal thrush)-      tinea capitis
Nystatin, fluconazole etc.          Treatment:
                                    • Topical-
                                    • Systemic-Terbinafine,
                                       griseofulvin or itraconazole
Anti Protozoals
 Amoebiasis & Giardiasis
 Malaria
 Kala-azar
 Uncomplicated Malaria            Uncomplicated Malaria
    Confirmed:                      Presumptive:
•   Tab. Co-artem 24 tablets in   • Cholorquine
    6 divided doses               Tab. 150 mg base
•   Tab Quinine for 7 days        Day 1: 4 tabs
                                  Day 2: 4 tabs
Alternative regimen:              Day 3: 2 tabs
• Quinine for 7 days +
   Tetracycline (250 mg 6
   hourly) for 7 days
• Quinine for 7 days +
   Doxycycline (100 mg 12
   hourly) for 7 days
 Severe Malaria:
Loading dose: Quinine dihydrochloride 20mg salt/kg body wt by
  infusion in 5% D/A over 4 hours

Maintenance dose: 8 hours after loading dose, maintenance
  10mg/kg body wt in 5% D/A over 4 hours. This should be
  repeated 8 hourly upto 6 doses (including loading dose). Then
  the quinine dose will be reduced to 5-7 mg salt/kg body wt until
  the patient can take oral medication.

If patient can take orally properly: Oral quinine sulphate 10mg
    salt/kg 8 hourly to complete a 7 day course of treatment

 Vivax Malaria:
Chloroquine 3 days + Primaquine 14 days
 Treatment Plan A                   Treatment Plan C
  Miltefosine 2.5mg/kg body wt      In kala-azar treatment failure or
  in 2 divided doses, orally, in        in pregnancy, amphotericin
  morning and evening after             B is the drug of choice.
  meal for 28 days.                 • Non liposomal (amphotericin
 Treatment Plan B                      B deoxycholate) 1mg/kg
  If miltefosine is not available       body wt. daily i.v. for 20 days
  or in kala-azar treatment             in 5% dextrose.
  failure, sodium antimony          • Liposomal amphotericin B 3
  gluconate 20 mg/kg body wt.           mg/kg body wt. i.v. daily for 5
  i.m. or i.v. for 30 days is to        days.
  be given.
 Treatment Plan D
Indication: Post Kala-azar Dermal Leishmaniasis.
Drug of choice: Sodium antimony gluconate 20mg/kg
   body wt i.m. or i.v. for 20 days per cycle; 6 cycles
   with 10 days interval between the cycles.

Alternative drug: Liposomal amphotericin B 3mg/kg
   body wt. i.v. for 5days per cycle; or Non liposomal
   amphotericin B1mg/kg body wt. for 15 days per cycle;
   6cycles with 10 days interval between the cycles
Anti helminths
 Gastro-Intestinal:
• Ancylostoma, Ascaris:
  Albendazole 400 mg single dose or
  Mebendazole 100 mg 12 hourly for 3 days

 Tissue parasite:
• Filariasis: Caused by Wuchereria bancrofti
• Treatment: Diethylcarbamazine 6 mg/kg body
  wt. orally in 3 divided doses for 12 days.
Renal dosing of commonly used
Antibiotics       Usual dosage            Renal dosage
amoxicillin po    250-500mg 8-12h         >30:no change 10-
                                          30:12h <10:24h
amoxicillin/      250/125 to 500/125 8h   >30:no change
clavulanate po                            10-30:12h

ceftriaxone iv    1-2g 24h                no adjustment

cefuroxime po     250-500mg 12h           >30:no change
                                          10-29: 12-24h
                                          <10: 250mg 24h
erythromycin po   250-500mg 6-12h         >/=10:no change
                                          <10: 50-75%of dose at
                                          same interval
Renal dosing of commonly used
Antibiotics                 Usual dosage           Renal dosage
clarithromycin po           250-500mg 12h          >/=30:no change
                                                   <30:500 mgx1, then
                                                   250mg 12-24h
azithromycin po             500mg x1, then 250mg   no adjustment
                            daily x4days
Tetracycline po             250-500 6h             >/= 50: no change
** Avoid if possible due                           10-50: q12-24h
to risk of liver toxicity                          <10: q24h
doxycycline                 100mg 12h              no renal adjustment

ciprofloxacin po            250-750mg 12h          >/=30:no change
                                                   <30: 24h
Renal dosing of commonly used
Antibiotic            Usual dosage     Renal dosage
Ciprofloxacin iv      200-400mg 12h    >/=30:no change
levofloxacin po/iv    500mg 12h        >/= 50: no change
                                       20-49: 500mg x1, then
                                       250mg 24h
                                       10-19: 500mg x 1, then
                                       250m 48h
metronidazole po/iv   500mg 6-8h       >/= 10: no change
adjust for hepatic                     <10: 500mg 8-12h
isoniazid             300mg po daily   no renal adjustment

rifampicin po/iv      600mg 24h        >/=10:no change
                                       <10: may give half
                                       usual dose
Renal dosing of commonly used
Antibiotic          Usual dosage     Renal dosage

ethambutol          15-25mg/kg 24h   >/=10:no change

acyclovir iv        5-10mg/kg 8h     >50: no change
                                     30-50: 5-10mg/kg 12h
                                     10-30: 5-10mg/kg 24h
                                     <10: 2.5-5mg/kg 24h
fluconazole po/iv   100-400mg 24h    >50: no change
                                     20-50: 1/2 usual dose
                                     <20: 1/4 dose 24h, or
                                     1/2 48h
 Davidson’s Principles and Practices of
  Medicine, 20th Ed
 Clinical Pharmacology, P.N.Bennet,
  M.J.Brown, 9th Ed
 Basic and Clinical Pharmacology, Katzung,
  11th Ed