Thursday, January 14, 2016

Antibiotic Choices for P. aeruginosa Infections

PRIMARY REGIMENS : IV ANTIBIOTICS
Antibiotics Class
Dosage range
Dosage Adjustment
Penicillins
Ticarcillin-clavulanate
3.1g q4h
CrCL <50 = 3.1g bd/tds
CrCL <10 = 2g bd
Piperacillin-tazobactam
4.5g q6h
CrCL >40 = 4.5g qid
CrCL <40 = 3.375g qid
CrCL <20 = 2.25g qid
Cephalosporins
Ceftazidime
2g tds
CrCL >50-90 = 2g bd/tds
CrCL <50 = 2g od/bd
CrCL <10 = 2g od or eod
Cefoperazone
2g bd

Cefepime
2g tds
CrCL >60 = 2g bd/tds
CrCL <60 = 2g bd
CrCL <30 = 2g od
CrCL <11 = 1g od
Monobactam
Aztreonam
2g tds
CrCL > 50-90 = 2g tds
CrCL <50 = 1-1.5g tds
CrCL <10 = 500mg tds
Fluoroquinolones
Ciprofloxacin
400mg tds
CrCL >50-90 = 400mg bd
CrCL <50 = 400mg od
CrCL <10 = 400mg od
Levofloxacin has no advantage over ciprofloxacin in term of coverage. Levofloxacin primarily indicated for Respiratory Tract Infection. But 750mg/day can be used in polymicrobial infection susceptible to streptococci and P. aeruginosa.
Other agents are not recommended (eg: Moxifloxacin)
Carbapenems
Meropenem
1g tds
CrCL >50-90 = 1g tds
CrCL <50 = 1g bd
CrCL <25 = 0.5g bd
CrCL <10 = 0.5g od
Doripenem
500mg tds
CrCL >50 = No adjustment
CrCL <50 = 250mg tds
CrCL <30 = 250mg bd
MIC:
Doripenem< Meropenem < Imipenem
Imipenem less recommended due to higher risk of resistance developing during treatment
*All agents associated with resistance emergence thus reserved in cases resistant to all other agents or polymicrobial infections
Other antibiotics


Colistin (Polymyxin E)
3MU(240mg) tds (NAG), 2.5 – 5mg/kg/day of CBA in 2-4 divided doses (Lexicomp) equivalent to 6.675mg – 13.35mg/kg/day of CMS in 2-4 divided doses
12,500IU CMS=1mg CMS
2.67mg CMS=1mg CBA
CrCL >50 = No adjustment
CrCL <50 = 3MU (240mg CMS) bd
CrCL <20 = 3MU (240mg CMS) od (Antibiotics Guidelines)
Polymyxin B
IV Loading 2.5mg/kg then 12 hours later 1.5mg/kg.Repeat q12h
10,000IU = 1mg
No renal adjustment
Used in treatment of MDR P.aeruginosa

ORAL ANTIBIOTICS: Only Fluoroquinolones
DRUGS
DOSING
DOSAGE ADJUSTMENT
Ciprofloxacin
750mg q12h
CrCL >50-90 = 500 – 750mg bd
CrCL <50 = 250 – 500mg bd
CrCL <10 = 500mg od
Levofloxacin
750mg od
CrCL >50-90 = 750mg od
CrCL <50 = 750mg q48h
CrCL <20 = 750mg once then 500mg q48h

ALTERNATIVE REGIMENS
DRUGS
DOSING
DOSAGE ADJUSTMENT
Imipenem-cilastatin
IV 500mg qid
CrCL >50-90 = 500mg qid
CrCL <50 = 250mg bd/tds

CrCL <10 = 125-250mg bd
Tobramycin
IV Loading dose of 7mg/kg then 5.1mg/kg od
CrCL <80 = 4mg/kg od
CrCL <60 = 3.5mg/kg od
CrCL <40 = 2.5mg/kg od
CrCL <30 = 4mg/kg q48h
CrCL <20 = 3mg/kg q48h

CrCL <10 = 2mg/kg q72h AD
Gentamicin
IV Loading dose 7mg/kg then 5.1mg/kg od
CrCL <80 = 4mg/kg od
CrCL <60 = 3.5mg/kg od
CrCL <40 = 2.5mg/kg od
CrCL <30 = 4mg/kg q48h
CrCL <20 = 3mg/kg q48h

CrCL <10 = 2mg/kg q72h AD
Amikacin*
IV 15mg/kg od
CrCL <80 = 12mg/kg od
CrCL <60 = 7.5mg/kg od
CrCL <40 = 4mg/kg od
CrCL <30 = 7.5mg/kg q48h
CrCL <20 = 4mg/kg q48h

CrCL <10 = 3mg/kg q72h AD
Aminoglycosides are used only in combination with a beta-lactam or fluoroquinolones (except for UTI)
Aminoglycosides can be stopped after 3-5 days in patient on combination therapy who are responding to treatment.
*Maybe active even if Gentamicin and Tobramycin resistant



Empiric therapy
  • Usage of two agents from different classes with in vitro activity against P. aeruginosa are recommended for empiric treatment of serious infections known or suspected to be caused by P. aeruginosa when there is high risk of antimicrobial resistance or when they occur in hosts for whom inappropriate antibiotic therapy would likely be associated with an especially high mortality.
  • Classic combination is high dose Piperacillin/Tazobactam + Gentamicin/ Tobramycin
  • Combination therapy increase the likelihood that at least one drug is active
Directed therapy 
  • Once results of susceptibility are available, definitive therapy can be tailored accordingly. 
  • For most infections, definitive therapy with a single active agent is appropriate, as there is no convincing clinical data that demonstrate a mortality benefit to combination therapy.
National Antibiotic Guideline 2014
INFECTIONS
PREFERRED
ALTERNATIVE
Pyonephrosis/ Perinephric  Abscess
IV Augmentin 1.2g tds + IV Gentamicin 5mg/kg od 
OR
IV Cefoperazone 1g bd
IV Ciprofloxacin 200-400mg bd
Renal Abscess
IV Unasyn 1.5g tds followed by 375mg PO bd
Or
IV Cefuroxime 750-1500mg tds followed by 250mg PO bd
PLUS/MINUS
Gentamicin 5mg/kg od (min 2weeks)
Ceftriaxone 1-2g od
Prostatic Abscess
IV Ciprofloxacin 200-400mg bd followed by 500mg PO bd min of 2-4 weeks
IV Cefoperazone 1g bd followed by Cefuroxime 500mg PO bd min 2-4 weeks
Epididymo-orchitis
Ciprofloxacin 500mg PO bd min of 2 weeks

Testicular Abscess
IV Augmentin 1.2g tds
Or
IV Unasyn 1.5g tds
IV Cefoperazone 1g bd

Urosepsis
IV Cefepime 1g bd
Or
IV Imipenem/Cilastatin 500mg tds
IV Cefoperazone/Sulbactam 1g
Diabetic Foot Infection
IV Tazocin 4.5mg tds/qid

Necrotizing Fasciitis
IV Cefoperazone 1g bd + IV Metronidazole 500mg tds
IV Cefoperazone/Sulbactam 1g bd + IV Metronidazole 500mg tds
Or
IV Tazocin 4.5g tds
Burn Wound Sepsis
IV Tazosin 4.5g tds/qid
IV Cefepime 1-2g tds
Bites
Duration of Tx= 10 days
PO Augmentin 625mg tds
PO Doxycycline 100mg bd + PO Clindamycin 300mg qid
IF SEVERE
IV Unasyn 1.5-3g tds/qid
OR
IV Tazosin 4.5g tds

REFERENCES
1. www.uptodate.com
2. Sanford Guide to Antimicrobial Therapy
3. National Antibiotics Guidelines 2014
4. Guide to Antimicrobial Therapy in the Adult ICU 2012
5. Lexicomp

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