ANTI PSEUDOMONAL DRUGS

Pseudomonal infections are treated with a combination of an antipseudomonal beta-lactam (eg, penicillin or cephalosporin) and an aminoglycoside. Carbapenems (eg, imipenem, meropenem) with antipseudomonal quinolones may be used in conjunction with an aminoglycoside. With the exception of cases involving febrile patients with neutropenia, in whom monotherapy with ceftazidime or a carbapenem (eg, imipenem, meropenem) is used, a 2-drug regimen is recommended.

Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Gentamicin
Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous. Adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.
• Dosing

Adult
Serious infections and normal renal function: 3 mg/kg/d IV q8h
Loading dose: 1-2.5 mg/kg IV q8h
Maintenance dose: 1-1.5 mg/kg IV q8h
Extended-dosing regimen for life-threatening infections: 5 mg/kg/d IV/IM q6-8h
Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion
Pediatric
<5 years: 2.5 mg/kg/dose IV/IM q8h
>5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults
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Ticarcillin and clavulanate

Inhibits biosynthesis of cell wall and is effective during stage of active growth. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes.
• Dosing

Adult
3.1 g IV q4-6h
Pediatric
75 mg/kg IV q6h
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Piperacillin and tazobactam

Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall and is effective during stage of active multiplication.
• Dosing

Adult
3.375 g IV q6h
Pediatric
75 mg/kg IV q6h
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Imipenem and cilastatin

Extremely potent broad-spectrum beta-lactam antibiotic. Rapidly hydrolyzed by enzyme dehydropeptidase I located on brush border of renal tubular cells, hence its combination with cilastatin (a reversible inhibitor of dehydropeptidase I). For treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated due to potential for toxicity.
• Dosing

Adult
Base initial dose on severity of infection and administer in equally divided doses
250-500 mg IV q6h; not to exceed 3-4 g/d
500-750 mg IM or intra-abdominally q12h
Pediatric
<12 years: Not established; 15-25 mg/kg/dose IV q6h suggested for > 3 mo
Fully susceptible organisms: Not to exceed 2 g/d
Moderately susceptible organisms: Not to exceed 4 g/d
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Aztreonam

Monobactam that inhibits cell wall synthesis during bacterial growth. Active against gram-negative bacilli but very limited gram-positive activity and not useful for anaerobes. Lacks cross-sensitivity with beta-lactam antibiotics. May be used in patients allergic to penicillins or cephalosporins.
• Dosing

Adult
500-2000 mg IV/IM q8-12h
Pediatric
90-120 mg/kg/d IV/IM divided q6-8h
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Ciprofloxacin

Exerts bactericidal effect against both actively dividing and dormant bacteria. Fluoroquinolone effective against pseudomonads, streptococci, some MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Trovafloxacin (Trovan) overcomes many of these limitations but has been removed from general use. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms disappear.
• Dosing

Adult
250-750 mg PO q12h
400 mg IV q8h
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
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Cefepime

For the treatment of Pseudomonas infections. Fourth-generation cephalosporin. Gram-negative coverage comparable to ceftazidime but has better gram-positive coverage. Cefepime is a zwitterion that rapidly penetrates gram-negative cells. Best beta-lactam for IM administration. Poor capacity to cross blood-brain barrier precludes use for treatment of meningitis.
• Dosing

Adult
1-2 g IV q12h; pseudomonal infections require higher or more frequent doses
Dosage adjustments (adult adjustments)
CrCl (mL/min) 80-50: 0.5-2 g IV q12-24h
CrCl 50-10: 0.5-2 g/d IV
CrCl <10: 0.25-0.5 g/d IV
HD: as for CrCl <10, with an extra 0.25 g after HD
During peritoneal dialysis: 1-2 g IV q48h
Pediatric
50 mg/kg IV q8h; not to exceed 2 g/dose
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Ceftazidime

Third-generation cephalosporin with high activity against Pseudomonas. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
• Dosing

Adult
1-2 g IV/IM q8-12h; not to exceed 6 g/d
Pediatric
Neonates: 30 mg/kg IV q12h
Infants and children: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d
Adolescents: Administer as in adults
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Tobramycin

Obtained from Streptomyces tenebrarius. Two to 4 times more active against pseudomonal organisms as compared to gentamicin.
• Dosing

Adult
Endocarditis: 8 mg/kg/d IV divided q8h; alternatively, 1 mg/kg IV q8h
Pediatric
6-7.5 mg/kg/d IV divided tid/qid (2-2.5 mg/kg q8h or 1.5-1.9 mg/kg q6h)
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Meropenem

Semisynthetic carbapenem antibiotic that inhibits bacterial cell wall synthesis.
• Dosing

Adult
1 g IV q8h
Pediatric
<10 years: Not established
>10 years: Administer as in adults