Medication Summary
Clinical trials are unavailable to assess optimal therapy. Treatment recommendations are based on results with similar gram-negative pathogens. Initiate treatment with an extended-spectrum antipseudomonal cephalosporin or penicillin combined with an aminoglycoside. Preferred beta-lactam antibiotics include cefepime, ceftazidime, aztreonam, piperacillin, and piperacillin-tazobactam. Carbapenems (ie, imipenem, meropenem) and intravenous fluoroquinolones are reserved for resistant cases.
Modify therapy based on the susceptibility test results. Uncomplicated infections often respond to monotherapy. Combination therapy with 2 antibiotics (choice based on susceptibility of organism) is preferred for complicated disease and immunocompromised patients. Duration of therapy should be appropriate for the clinical syndrome.
Cephalosporins
Class Summary
Many nosocomial M morganii strains express derepressed chromosomal ampC beta-lactamases (Bush group 1) similar to those produced by P aeruginosa and Enterobacter species. These strains may be resistant to ceftazidime and other third-generation cephalosporins but are usually susceptible to cefepime, imipenem, meropenem, piperacillin, aminoglycosides, and fluoroquinolones. The beta-lactamase inhibitors (ie, clavulanic acid, sulbactam) are ineffective against these enzymes; however, the combination of piperacillin and tazobactam is more effective than piperacillin alone. Rare isolates of M morganii produce ESBLs. ESBLs hydrolyze drugs (eg, ceftazidime, cefotaxime, aztreonam) but have little effect on the cephamycins (eg, cefoxitin, cefotetan). ESBLs are inhibited by clavulanic acid.
Cefepime (Maxipime)
Fourth-generation cephalosporin. Gram-negative coverage comparable to ceftazidime but has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitter ion; it rapidly penetrates gram-negative cells. Stable against rare isolates of M morganii, which produce ESBLs. Also stable against the more common M morganii isolates with derepressed chromosomal ampC beta-lactamases (Bush group 1).
Penicillins
Class Summary
Many nosocomial M morganii strains express derepressed chromosomal ampC beta-lactamases (Bush group 1). These strains usually are susceptible to piperacillin; however, the combination of piperacillin and tazobactam is more effective. Beta-lactamase inhibitors (eg, clavulanic acid, sulbactam) are ineffective against these enzymes.
Piperacillin-tazobactam (Zosyn)
Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.
Aminoglycosides
Class Summary
These agents bind irreversibly to 30S bacterial ribosomes, thus inhibiting synthesis of proteins. They are bactericidal. They demonstrate concentration-dependent killing and postantibiotic effect (PAE). These latter 2 properties have been instrumental in designing high-dose, extended-interval dosing regimens (ie, high serum concentrations saturate bacterial receptors, resulting in rapid bacterial killing). High doses are administered q24h (or longer), which allow adequate drug clearance. Despite drug elimination, bacterial regrowth is not observed (PAE). These regimens are equivalent or superior to conventional dosing in effectiveness and safety. Extended-interval regimens are also effective in patients with neutropenia.
Aminoglycosides are less effective in anaerobic or acidic environments because their transport (energy and oxygen dependent) is inhibited. Uptake is facilitated by bacterial cell wall synthesis inhibitors (ie, beta-lactams, vancomycin). They are administered parenterally to treat serious infections. They are highly polar; thus, they have low intracellular concentrations and cross the blood-brain barrier poorly. Other tissues where concentrations are suboptimal include eye, bone, and prostate.
Gentamicin (Garamycin)
Considered aminoglycoside of choice because of its low cost. Indicated for empiric treatment of life-threatening infections.
Carbapenems
Class Summary
These agents are bactericidal broad-spectrum antibiotics that inhibit cell wall synthesis. Bicyclic beta-lactams are effective against most gram-positive, gram-negative, and anaerobic bacteria.
Meropenem (Merrem)
Slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci, compared to imipenem. Unlike imipenem, does not require a dehydropeptidase inhibitor (cilastatin). Has superior penetration of blood-brain barrier compared to imipenem. Useful to treat meningitis.
Monobactams
Class Summary
These agents are monocyclic beta-lactam antimicrobials with activity only against aerobic gram-negative bacilli. Monocyclics can be used safely in patients with bicyclic beta-lactam hypersensitivity. No oral form is currently available. They are effective antibiotics; however, they are potent inducers of beta-lactamase production. Because of this, many hospitals restrict their use.
Aztreonam (Azactam)
Structurally similar to ceftazidime. Inhibits cell wall synthesis during bacterial growth.
Fluoroquinolones
Class Summary
These are synthetic broad-spectrum antibacterial compounds. They have a novel mechanism of action, targeting bacterial topoisomerases II and IV, thus leading to a sudden cessation of DNA replication. Oral bioavailability is greater than 90%. Genetic barrier to resistance is not great (only 1-2 mutations).
Levofloxacin (Levaquin)
Useful for infections due to multidrug-resistant gram-negative organisms, but drug of choice for only a few infections.
