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      Drugs & Diseases > Infectious Diseases

      Enterobacter Infections Medication

      Updated: Jun 02, 2022
      • Author: Susan L Fraser, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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      Medication

      Medication Summary

      The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications. Before prescribing, and during therapy, always check for renal dose adjustments.

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      Antibiotics

      Class Summary

      The antimicrobials most commonly indicated in Enterobacter infections include carbapenems, fourth-generation cephalosporins, aminoglycosides, fluoroquinolones, and TMP-SMZ.

      Carbapenems continue to have the best activity against E cloacae, E aerogenes, (now known as Klebsiella aerogenes) and other Enterobacter species. [68] They are not affected by ESBLs. Imipenem-cilastatin and meropenem are used most often. Ertapenem, approved more recently, is gaining clinical experience [69] but emerging resistance is a growing concern. [70] Doripenem, approved in the United States in 2007, appears to be as effective as the other carbapenems. In August 2017, meropenem/vaborbactam (Vabomere) was approved for complicated urinary tract infections (cUTIs), including pyelonephritis, caused by susceptible Enterobacteriaceae: E coli, K pneumoniae, and E cloacae species complex. [49]

      First-generation and second-generation cephalosporins are inactive against Enterobacter infections. Third-generation cephalosporins frequently show good in vitro activity against these organisms, but, as explained above, a significant risk of developing full resistance during therapy exists. Resistance develops much less frequently with fourth-generation cephalosporins because they are relatively stable to AmpC beta-lactamase but not (so far) to the less frequently encountered ESBLs (see Medical Care). Third-generation cephalosporins are not indicated for the treatment of severe Enterobacter infections, perhaps with the notable exception of uncomplicated infections.

      Fluoroquinolones have good bactericidal activity against gram-negative bacilli; their bioavailability ranges from very good to excellent (with the exception of norfloxacin). Newer quinolones have increased their spectrum toward gram-positive organisms and, in some cases, toward anaerobes. Ciprofloxacin and levofloxacin have the best activity against gram-negative bacilli and should generally be selected over the newer fluoroquinolones if clinically indicated.

      Polymyxin B

      Binds to phospholipids, alters permeability, and damages bacterial cytoplasmic membrane.

      Ciprofloxacin (Cipro)

      Fluoroquinolone with good activity against pseudomonads and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Among fluoroquinolones, ciprofloxacin has the best activity against the gram-negative bacilli (including Enterobacter). IV and PO formulations available. Oral bioavailability is approximately 80%.

      Levofloxacin (Levaquin)

      Levofloxacin is an alternative to ciprofloxacin. It has the advantage of once daily dosing, whether administered IV or PO.

      Used for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.

      Doripenem (Doribax)

      Carbapenem antibiotic. Doripenem is a new alternative choice. Has spectrum of activity similar to that of imipenem and meropenem.

      Elicits activity against a wide range of gram-positive and gram-negative bacteria. Indicated as a single agent for complicated intra-abdominal infections caused by susceptible strains of E coli, K pneumoniae, P aeruginosa, Bacteroides caccae, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Streptococcus intermedius, Streptococcus constellatus, and Peptostreptococcus micros.

      Imipenem/cilastatin (Primaxin IV)

      For treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential toxicity. DOC for severe Enterobacter infections, except for meningitis and other CNS infections because of some reports indicating higher seizure potential. Hydrolyzed by the renal dehydropeptidase-1. To overcome this urinary inactivation, cilastatin, an inhibitor of this renal enzyme, is administered in equal amounts.

      Meropenem (Merrem IV)

      Alternative to imipenem for severe Enterobacter infections. Carbapenem of choice for meningitis and for patients at risk for seizures. Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Effective against most gram-positive and gram-negative bacteria. Not degraded by renal dehydropeptidase-1. Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem.

      Cefepime (Maxipime)

      Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage.

      Meropenem/vaborbactam (Vabomere)

      Indicated for complicated urinary tract infections (cUTI) caused by carbapenem-resistant Enterobacteriaceae (CRE). Vaborbactam is a nonsuicidal beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases such as K pneumoniae carbapenemase (KPC). Vaborbactam does not have any antibacterial activity and does not decrease the activity of meropenem against meropenem-susceptible organisms.

      Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS)

      Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except P aeruginosa. Susceptibility of Enterobacter is generally good but varies among centers.

      Ertapenem (Invanz)

      Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. Stable against hydrolysis by various beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.

      Tigecycline (Tygacil)

      FDA approved for complicated intra-abdominal or skin and soft-tissue infections. A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Complicated intra-abdominal infections caused by C freundii, E cloacae, E coli, K oxytoca, K pneumoniae, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible isolates only), S anginosus group (includes S anginosus, S intermedius, S constellatus), B fragilis, B thetaiotaomicron, B uniformis, B vulgatus, C perfringens, and P micros.

      Ceftazidime/avibactam (Avycaz)

      A new cephalosporin beta-lactamase–inhibitor antibiotic with extended activity against many gram-negative bacilli. Avibactam is a member of a novel class of non–beta-lactam beta-lactamase inhibitors, the diazabicyclooctanes (DBO), acting as a reversible covalent inhibitor. Compared to available inhibitors for clinical use, DBOs are more potent, have a broader spectrum, and have a different mechanism of action. A unique feature of avibactam in contrast to earlier beta-lactamase inhibitors is that avibactam binds reversibly to beta-lactamases, allowing for recyclization and inhibition of additional beta-lactamase molecules. Avibactam effectively inactivates class A (ESBLs and KPC), class C (AmpC), and some class D (eg, OXA-48) beta-lactamases.

      Eravacycline (Xerava)

      Eravacycline is a fluorocycline antibacterial drug within the tetracycline class. Has expanded activity compared to tigecycline. Available for parenteral administration only. Not approved for use in children.

      Plazomicin (Zemdri)

      Plazomicin is an aminoglycoside antibacterial indicated for the treatment of complicated urinary tract infections (CUTI), including pyelonephritis, in patients aged 18 years or older. As only limited clinical safety and efficacy data are available, it is reserved for use in patients who have limited or no alternative treatment options. To reduce the development of drug-resistant bacteria and maintain effectiveness of plazomicin and other antibacterial drugs, it should be used only to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms. Dosing adjustments are required in patients with renal impairment.

      Colistimethate (Coly Mycin M)

      Parenteral formulation indicated for the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli. It is particularly indicated when the infection is caused by sensitive strains of Pseudomonas aeruginosa. Not indicated for Proteus or Neisseria infections. Coly-Mycin M Parenteral has proven clinically effective in the treatment of infections due to the gram-negative organisms Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, and P aeruginosa.

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      siderophore cephalosporin

      cefiderocol

      A new class of antibiotic: an injectable siderophore cephalosporin that combines a catechol-type siderophore and cephalosporin core with side chains similar to cefepime and ceftazidime. This structure and its unique mechanism of action confer enhanced stability against hydrolysis by many beta-lactamases. It is active against many gram negative bacilli, including both fermenter and non-fermenters. It is not active against gram positive or anaerobic organisms.

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      Monobactams

      Class Summary

      Aztreonam has activity against some Enterobacter isolates, but not usually against more resistant strains. Laboratory testing must be done to confirm sensitivity to this drug before using it alone to treat serious infections. It has been combined with avibactam to broaden its activity against carbapenemase producing isolates, but the drug is not yet FDA approved. It has been used in combination with ceftazidime-avibactam to treat bloodstream and other serious infections caused by metallo-β-lactamase producing Enterobacterales.

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