Medication Summary
Pseudomonas should be considered in the differential diagnoses in any probable Gram-negative infections. Often, the effect of this organism causes concern because it can cause severe hospital-acquired infection, especially in immunocompromised hosts. Furthermore, a concomitant antibiotic resistance is often present, which makes the choice of treatment difficult.
Often, treatment initially consists of empiric antibiotics. Therefore, when treating Pseudomonas organisms, one must consider some basic concepts. Indwelling catheters associated with any infections should be promptly removed. Delays in treatment are associated with high mortality. Combination therapy needs to be initiated in patients with severe infections and high-risk patients. Combination therapy requires 2 antipseudomonal antibiotics, each with different mechanisms of action. Often, treatment is achieved with a combination of an aminoglycoside or quinolone with another antipseudomonal antibiotic.
Combination therapy with antipseudomonal antibiotics is used to ensure treatment of resistant strains and to prevent selection of resistant mutants. Carbapenems (eg, imipenem, meropenem) and the monobactam antibiotic aztreonam are generally reserved for serious infections caused by organisms resistant to other beta-lactam antibiotics or in those with renal disease who are at risk for aminoglycoside-related nephrotoxicity.
Previous animal studies had brought concern of the use of quinolone in children. However, the use of quinolone is now being revisited. [13] Discussion of these previous animal studies with
parents may be warranted.
Some exceptions to double-coverage antibiotics include the treatment of simple urinary infection (eg, cystitis) or local skin infection or empiric antibiotic coverage in the febrile patient with neutropenia. However, one of the most controversial topics in management involves combination versus monotherapy treatment. Well-designed studies are still needed to settle this controversy. If monotherapy is chosen, certain antibiotics (eg, aminoglycosides, aztreonam) should not be used as empiric monotherapy.
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the clinical setting. Whenever feasible, select antibiotics based on culture sensitivity. Review of the institution's resistance is essential.
Ceftazidime (Ceptaz, Fortaz, Tazidime, Tazicef)
DOC for pseudomonal CNS infections and melioidosis. Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Cefepime (Maxipime)
Along with ceftazidime, DOC for CNS infections. Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage.
Meropenem (Merrem IV)
Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococcal and streptococcal organisms compared to imipenem.
Imipenem and cilastatin (Primaxin)
Treats multiple organism infections when other agents do not have wide spectrum coverage or are contraindicated because of potential for toxicity.
Piperacillin and tazobactam (Zosyn)
Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.
Ticarcillin and clavulanate (Timentin)
Inhibits biosynthesis of cell wall mucopeptide and is effective during active growth stage. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive, gram-negative, and anaerobic organisms.
Tobramycin (Nebcin)
Used in skin, bone, and skin structure infections, caused by S aureus, P aeruginosa, Proteus species, Escherichia coli, and Klebsiella and Enterobacter species.
Gentamicin (Garamycin)
Aminoglycoside antibiotic for gram-negative coverage, used in combination with agents against gram-positive organisms and anaerobes.
Often not DOC, yet consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, or in mixed infections caused by susceptible staphylococcal and gram-negative organisms. Base choice between tobramycin and gentamicin on the susceptibility of the area.
DOC for pediatric pseudomonal UTI.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM; once-a-day dosing is more effective.
Follow each regimen by at least a trough level drawn before the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after completion of 30-min infusion.
Ciprofloxacin (Cipro)
Fluoroquinolone with activity against pseudomonads, streptococcal, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. DOC for adult pseudomonal UTI and some skin infections.
Aztreonam (Azactam)
Monobactam, not beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. Is active against gram-negative bacilli but has very limited gram-positive activity and is not useful for anaerobes. Lacks cross-sensitivity with beta-lactam antibiotics. May be used in patients allergic to penicillins or cephalosporins.
Duration of therapy depends on the severity of the infection; therapy is continued for at least 48 h after the patient is asymptomatic or evidence of bacterial eradication has been obtained. Doses smaller than indicated should not be used. Transient or persistent renal insufficiency may prolong serum levels. After initial loading dose of 1 or 2 g, reduce dose by one half for estimated ClCr of 10-30 mL/min/1.73 m2. When only serum creatinine concentration available, the following formula (based on sex, weight, age) can approximate ClCr. Serum creatinine should represent a steady state of renal function.
Males: ClCr = [(weight in kg)(140 - age)] / (72 X serum creatinine in mg/dL).
Females: 0.85 X above value. In patients with severe renal failure (ClCr < 10 mL/min/1.73 m2) and those supported by hemodialysis, the usual dose of 500 mg, 1 g, or 2 g is given initially.
Maintenance dose is one fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 h.
For serious or life-threatening infections, supplement maintenance doses with one eighth of the initial dose after each hemodialysis session.
Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by kidneys, obtain estimates of ClCr and make appropriate dosage modifications. Insufficient data are available in regard to IM administration to pediatric patients or dosing in pediatric patients with renal impairment. Administered IV only to pediatric patients with normal renal function.
Streptomycin
Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated. For treatment of susceptible infections and glanders infection.
Trimethoprim and sulfamethoxazole (Bactrim, Septra)
DOC for B cepacia. Dihydrofolate reductase inhibitor that prevents tetrahydrofolic acid production in bacteria. Active in vitro against a broad range of gram-positive and gram-negative bacteria. Resistance is usually mediated by decreased cell permeability or alterations in amount or structure of dihydrofolate reductase. Demonstrates synergy with sulfonamides, potentiating inhibition of bacterial tetrahydrofolate production. Trimethoprim provides a synergistic effect when combined with sulfas.
Tetracycline (Sumycin)
Treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits; DOC in combination with streptomycin for glanders infection.
Acetic acid otic (VoSoL Otic)
Effectively treats superficial bacterial infections of otitis externa.
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Erythematous papulopustules of pseudomonas folliculitis. Courtesy of Mark Welch, MD.
