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